Chemoradiation therapy and side effects. Oncology. Simultaneous use of radiation treatment and chemotherapy

In Russia, in the structure of general cancer incidence, genital tumors account for 14-20%. Evaluating the methods of treating common processes of cervical cancer, we can come to the conclusion that the main method of treatment is radiation therapy as an independent method and as a component of combined treatment. The question of chemoradiation treatment of endometrial cancer remains open and there remains a need for further research in this direction.

According to world statistics, 1/3 of all tumors in women and 16% of the total number of tumors of both sexes are breast cancer and cervical cancer. In Russia, in the structure of the general cancer incidence, genital tumors account for 14-20%. Of these, cervical cancer ranks second: the share of uterine cancer, cervical cancer and ovarian cancer is 6.2, 5.8 and 5.2%, respectively. At the same time, the standardized mortality rate from cervical cancer per 100,000 Russian women is 5.2; uterine cancer is 4.9 (Remennik L.V., Novikova E.G. et al., 1999). uterine cancer

Cervical cancer

IN last years The developed screening program for the early diagnosis of cervical cancer with the active identification of women suffering from background and precancerous processes, which ensured a noticeable reduction in the incidence of cervical cancer, was curtailed for a number of social and economic reasons, which in turn led to a significant increase in neglect rates.

In the practice of oncopathology, the situation is immutable - the more advanced the process, the fewer options for treatment benefits.

The issue of treatment of cervical cancer depending on the stage currently does not cause significant disagreement among researchers and clinicians in various clinics. Due to the younger age of these patients compared to other localizations of gynecological cancer, the issue of organ-preserving treatment is urgent. On the other hand, given the more autonomous and aggressive course compared to hormone-dependent tumors, the most radical treatment is necessary.

Three main treatment methods are used: surgical, combined and combined radiation therapy, and radiation is the leading method of treatment for cervical cancer and practically the only one possible for stage III of this disease.

However, analyzing the history of the development of physical and technical support for radiation therapy, conducting a retrospective analysis looking to the future through the eyes of a physicist, M.Sh. Weinberg (1994) notes that “there is no increase in the effectiveness of radiation therapy in proportion to the improvement of its physical and technical base. IN Lately It has been noted that its growth rate is decreasing, falling further and further behind the forecast associated with the use of new promising methods, technical and technological means (individualization, optimization, automation, computerization) in radiation therapy.”

Dissatisfaction with the results of treatment of patients with malignant tumors has led to the development of various options and methods that complement radiation therapy.

Methods of radio modification have been developed in the form of non-standard fractionation of the radiation dose, based on the concept of oxygen heterogeneity of tumor tissue (Pelevina I.I., Voronina S.S. et al., 1984). Along with this, a number of physical and chemical radiomodifiers with radioprotective and radiosensitizing properties have been proposed today. As a polyradiomodification of the radiosensitivity of a tumor and normal tissues, the following are used: hyperbaric oxygenation, tourniquet and general gas hypoxia by inhaling a gas mixture with an oxygen content reduced to 8-10% during a remote gamma therapy session, the use of laser units and other options.

To overcome the radioresistance of a number of tumors and enhance the effect of the ionizing effects of radiation, it is carried out in combination with electromagnetic, inductive UHF local hyperthermia (Yarmonenko S.P., 1995; Gavrilenko M.F., Ivankova V.S., et al., 1995) and general controlled hyperthermia (Plyaskin K.N., Tyulenev P.S. et al., 1996).

The possibilities of enhancing radiation damage to a tumor by creating short-term hyperglycemia with a decrease in tumor pH from 6.7 to 5.4 were studied. According to experimental data, Ulyanenko S.E., Polityukova N.A. (1991), it was found that the antitumor effect of irradiation at all doses of glucose decreases with increasing initial tumor volume.

The most common class of chemical radiomodifiers previously were electron-acceptor compounds, among which metro-misonidazole compounds showed high activity as radiosensitizers of hypoxic cells in in vitro experiments and in biological models.

Clinical trials have shown a definite trend towards improved treatment outcomes for lung cancer, esophageal cancer, head and neck tumors, Bladder and cervix with generally accepted methods of introducing metronidazole into the body (Mufazalov F.F., Nabiullina M.K. et al., 1992; Muravskaya G.V., Zharkov V.V. et al., 1995; Bleehen N.M., 1998) . The authors, however, point out the frequency of toxic reactions when using metronidazole, starting with a drug concentration in the blood of 120 mcg/ml, while the greatest radiosensitizing effect of the drug is achieved at a blood concentration of 170-220 mcg /ml (Balmukhanov S.B., Mustafin Zh.S., Filipenko V.I. et al., 1990; Polyakov P.Yu., Zamyatin O.A., Bychenkov R.A., 1996).

To reduce the toxicity of the drug, which is further enhanced in combination with radiation, a method of intratumoral and intraparametric administration of metronidazole has been developed during traditional combined radiation treatment of cervical cancer (Balmukhanov S.V. et al., 1990). The effectiveness of radiation therapy with intratumoral administration of metronidazole was expressed in accelerated (with a total dose of 36-56 Gy) and complete regression of the tumor in 54.3% of patients. In the control - radiation treatment without metronidazole, respectively, in 42%. At the same time, the 3-year survival rate of patients with stage III cervical cancer is 79.7±4.1%. Similar results of 2-3-year survival were obtained by Stolyarova I.V., Vinokurov V.L. et al., (1991, 1992); Demidova L.V., Teleus T.A. (1994).

Metronidazole was also used in the form of applications with dimexide sulfoxide, which promotes the accumulation of a radiosensitizer in tumor tissue in high concentrations to enhance the damaging effects of ionizing radiation (Zharinov G.M., 1993, 1997; Vinokurov V.L. et al., 1994). Moreover, after combined radiation treatment of 200 patients with cervical cancer, 5-year survival in stage III of the process was obtained in 59±4% of cases, in controls - 36±7% (Zharinov G.M. et al., 1995).

Cervical cancer is one of those tumors in which the possibilities of additional use of chemotherapy drugs are very limited due to their known insignificant effectiveness in this pathology (Perevodchikova N.I., 2005).

Advances in drug therapy in the creation of new cytostatics, the development of the principles of combination chemotherapy with cyclic sequential administration of antitumor drugs have led to a new wave of use medicines, including in the treatment of cervical cancer (Gershanovich M.L., Borisov V.I., Sidorenko Yu.S. et al., 1995; Tyulyandin S.A., 1998; Gorbunova V.A., Borisov N.B. et al., 1996; Shirasaka Tetsuhiko, Fukushima Masakazu, Kimura Kijoji, 1995).

However, the general toxic effects of maximum doses of modern cytostatics administered parenterally (subcutaneously, intramuscularly, intravenously, rectally) are quite pronounced. This is the limiting moment as with their independent use, and a serious obstacle to combined use with ionizing radiation, which is a factor that increases the risk of complications during chemotherapy (Bogush TA, Bogush EA, 1995; Muss Hyman B., Blessing John A. et al, 1992; Vanchieri C., 1992; Dargent D., Raudrant D., Berland T.M., 1994; Bloss J.D., Lucci J.A-3rd et al, 1995).

Using a combination of cytostatics (vincristine, platidiam and adriamycin) in the treatment of common cervical cancer processes, Zabunov A.V. and Dudareva LA (1991), noted complications in the form of nausea, vomiting in all patients, alopecia in 96.7%, suppression of hematopoiesis in 60% of cases, nephrotoxicity in 40%.

During chemoradiation treatment of patients with cervical cancer with the inclusion of 5-fluorouracil and mitomycin C in the treatment regimen, severe hematological complications of the third degree were observed in 5% of patients, dyspepsia in 4% of cases (Cole D.R., Jones A.C., 2003).

Comprehensive programs of chemo-radiation treatment of advanced cervical cancer with polyradiomodification options were also proposed. Before and/or during combined radiation therapy, carried out in the mode of non-traditional dose fractionation, the administration of 5-fluorouracil is used, supplemented by the administration of cisplatin (Demidova L.V. et al., 1994, 1996); or methotrexate in combination with UHF hyperthermia (Gavrilenko M.F. et al., 1995; Ivankova V.S., Evtushenko G.V., et al., 1996); or mitomycin C (Cole D. J., Jones A. C., 2003); or sisophora (Migazaki Kohji, Katabuchi Hidltaka et al, 1999).

Nevin J., Bloch B., Van Wijk L et al, (2005) conducted 3 courses of combination chemotherapy (cyclophosphamide, bleomycin, cisplatin) in 26 patients with stage III cervical cancer followed by radiation therapy. Partial tumor regression was noted in 44.5% of cases. 7 patients did not complete chemotherapy due to severe toxicity with 1 death. Authors' conclusion: Courses of chemotherapy for cervical cancer are ineffective, toxic, and have no survival benefit.

The same opinion is shared by Dargent D, Raudrant D et al (2000), Bloss J.D., Lucci JA.-3rd, Disaia R.J. et al (2001), presenting 3-year survival rates for patients with stage III cervical cancer after chemoradiotherapy with conventional methods of administering cytostatics within 60%.

Symonds R.P.,Watson E.R. et al (1998) obtained 3-year survival rates for stage III cervical cancer patients of 48%.

Using a combination of cytostatics (cisplatin, bleomycin, vincristine) before combined radiation therapy, 5-year survival of patients with advanced cervical cancer was achieved in 68% of patients (Zarcone R., Tartaglia E., Cardone G. et al, 2004).

Using hydroxyurea as a modifying agent during radiation therapy and after its completion in a continuous course for 4 weeks Piver M.S. et al., (1997), managed to achieve 60% 5-year survival of patients with stage III cervical carcinoma.

Peters W., (1999) using combined irradiation and parallel systemic administration of cisplatin and 5-fluoro-racil achieved 3-year survival in 87% of women with advanced cervical cancer.

In turn, Whitney C.W., (1999), Morris M., (1999), Rose P.G., (1999), Keys H.M., (1999), E. Vrdoljak T., (2003) based on the results of randomized trials, registered a significant increase in relapse-free survival patients receiving radiochemotherapy with cisplatin, hydroxyurea and 5-fluorouracil with acceptable toxicities, which ultimately served as a recommendation for the use of chemoradiotherapy as the standard of care for patients with cervical cancer.

The study of preoperative radiochemotherapy demonstrated its effectiveness in improving operability (Chang H.C., 1992, Fontanelli R., 1992, P. Benedetti Panici 1993).

On V International conference users of the Selectron system in The Hague J. Horiot et al, (1988); J. Stumpl et al, (1988) pointed out the need to develop research in the direction of using regional chemotherapy techniques in patients with gynecological oncological pathology.

Reports on the use of intra-arterial chemotherapy for advanced cervical cancer in addition to combined radiation therapy are heterogeneous. The clinical material of the studies is small in volume (groups of patients with stage III cervical cancer of 10-14 patients), the composition of the cytostatics used is different. However, the authors (Vinokurov V.L., Neklasova N.Yu., Zharinov G.M. et al., 1992; Vorobyova L.I., Dotsenko Yu.S., Vinnitskaya A.B. et al., 1996; Teterin K.A., Kizhaev E.V., 1996; Anfilov S.V., Selyuzhitsky I.V. et al., 1999; Jkeda M., Noda K., 2002; Narimatsu Akio, Ito Takehisa, 2005; Murakami Takahiro, Nagai Nobutaka Takehara et al, 2005; Itoh Miho, Murase Toshiko et al, 2005) positively assess the possibilities of regional intra-arterial polychemotherapy for cervical cancer, taking into account the immediate effectiveness of the method and the number of general toxic reactions - no higher than with the systemic use of cytostatics.

At the Federal State Institution "Research Institute of Oncology named after N.N. Petrov Rosmedtekhnologii" preoperative chemoradiotherapy has been used since 1997.

Treatment regimen

At the first stage of treatment, remote radiation exposure is performed on a linear electron accelerator LUEV-15M1 (Ex = 15 MeV). Uniform irradiation of the pelvis is performed from 2 opposing fields measuring 15x15 cm or 16x16 cm in the usual fractionation mode (ROD = 2 Gy daily 5 times a week to OD = 20-30 Gy at points A and B). For large exophytic tumors, 1-2 sessions of intracavitary irradiation are performed on the Microselectron VMD device from Nucletron (Holland) with a progressive stepwise movement of the Iridium-192 source.

We use two drugs as radiosensitizing agents: cisplatin (CDDP) and capecit-bin (Xeloda).

Cisplatin is administered intravenously once a week (for four weeks) at a rate of 20 mg/m2, up to a total dose of 120 mg. The basis for choosing the dose of the drug was the results of studies by R. Rose et al 1997 and H. Keys et al 1997, in which cisplatin was administered at a rate of 40 mg/m2. The dosage regimen we have chosen provides a significant increase in the effect of the first stage of treatment with acceptable toxic complications.

Capicetabine is administered at a dose of 2000 mg, daily, per os, during a two-week course of preoperative radiation exposure. Xeloda is a fluoropyrimidine carbamate derivative and, when activated in tumor tissue, has a selective cytotoxic effect on it. As a result of selective activation, the content of 5-FU in the tumor significantly exceeds its levels in healthy tissues, and thus the systemic exposure of 5-FU to healthy tissues of the body is reduced.

At the end of the first stage, a comprehensive assessment of the effectiveness of the treatment is carried out.

After 10-12 days, patients who could undergo radical surgical intervention underwent radical panhysterectomy with bilateral iliac lymphadenectomy using the Wertheim-Meigs method. The number of radically operated patients was 292 (87%) people. After the final morphological analysis of the surgical material with invasion of more than 5 mm and up to 1 cm and the absence of metastases to the regional lymph nodes, remote pelvic irradiation was performed from open fields ROD = 2 Gy to SOD = 10-14 Gy, in total at t. B 4244 Gy, taking into account the preoperative course. In case of invasion of more than 1 cm and the presence of metastatic lesions of regional lymph nodes, external irradiation was performed in the same fractionation mode, with a total of 50-55 Gy. In addition, after 4-5 weeks, adjuvant chemotherapy with cisplatin 20 mg/m2 in mono mode was carried out on days 1-5 (2 cycles with an interval of 4 weeks) or two cycles of chemotherapy with Xeloda in mono mode at the rate of 2500 mg/m2.

The remaining patients, for whom radical surgery cannot be performed due to insufficient effect, undergo combined radiation treatment. Irradiation of the pelvis is performed in the usual fractionation mode from 2 opposing fields of 15x15 cm or 16x16 cm. With an open field, doses of 20, 26, 30 Gy are delivered to the lesion at stages Ib2, IIb, III. Then a central shielding block is installed and the dose to the pelvic lymph nodes is adjusted to SOD = 46 Gy. at stage IIb-III.

Contact irradiation is carried out on the Microselectron VMD device in the fractionation mode: ROD = 7 Gy, once a week, SOD = 28 Gy.

5-6 weeks after the end of the course of combined radiation therapy, patients received two cycles of monochemotherapy CDDP 20 mg/m 2 with an interval of 4 weeks or two cycles of chemotherapy with capicetabine alone.

We assessed the clinical effect in the first week after the end of the first stage of treatment. By this time, patients in the group with CLL received 4 infusions of cisplatin (SD = 120 mg) or the total dose of capicetabine was 28,000 mg and the total focal dose at point A from external beam radiation therapy averaged 24 Gy, and the total focal dose at point A was 24 Gy on average. And for women in the control group it was 30 Gy.

In Fig. Figure 1 shows the characteristics of the primary clinical effect in the comparison groups.

As a result of the first stage of treatment, complete regression of the clinically visualized tumor lesion was noted in 15 (4.6%) patients in the study group and in 3 (0.9%) in the control group. A decrease of more than 50% from the initial size was recorded in 162 (48.3%) in the group with chemoradiation treatment at the first stage and in 122 (37.4%) patients with radiation therapy.

Regression of the tumor by more than 25%, but not exceeding 50%, was detected in 106 (31.4%) and 68 (21.1%) cases. 53 (15.7%) and 132 (40.6%) patients in the two comparison groups did not respond to therapy, respectively.

In general, we can say that an objective response after the first stage of treatment was achieved in 84.3% of patients in the study group and in 59.4% in the control group (p<0,01).

Additionally, it should be pointed out that in those cases where we stated the absence of an objective response (in the chemoradiation treatment group), certain positive changes took place: the exophytic part of the tumor decreased, its bleeding and volume of discharge decreased, the necrosis fields on the tumor decreased or completely disappeared. surface of the tumor, which undoubtedly indicated the effectiveness of the treatment.

Of great importance in determining the degree of spread of the tumor process and analyzing the effectiveness of treatment is data on the presence of infiltration of parametric tissue and the nature of its changes.

In table Table 1 presents information on the dynamics of parametrial infiltrates in the study and control groups.

From these data, despite their subjectivity, it becomes clear that targeted intrasystemic administration of cytostatics had a more noticeable effect on the specific infiltration of parametriums compared to the effect of irradiation alone.

Of 336 patients with stage IB2-III cervical cancer who received combined treatment according to the scheme: chemoradiotherapy - surgery - radiation therapy, 87% of patients were in remission for more than 3 years.

The number of radically operated patients was 292 (87%) people, 44 (13%) patients received combined radiation treatment.

One of the important limiting aspects of the use of cytostatic drugs in treatment regimens for patients suffering from malignant neoplasms is the presence of side toxic effects associated with the administration of these drugs. In this connection, an analysis of these manifestations was carried out in patients in the study group.

In table Table 2 shows data on the percentage and degree of complications encountered.

It should be noted that the degree of the most common complications did not exceed moderate.

In table Table 3 reflects information about the reactions of internal organs to chemoradiotherapy treatment.

From the presented data we can conclude that the nature and degree of early complications did not differ significantly in the comparison groups.

Since the patient’s quality of life is largely determined by the presence or absence of one or another late radiation complication, it is appropriate to say that the incidence of late radiation rectitis in the study group was 9.3% (in 31 women), late radiation cystitis occurred in 18 (5, 5%) of patients.

Cancer of the uterus

The rapidly developing problem of hyperplastic processes and endometrial cancer (EC) is of interest to many specialists. The increase in the incidence of uterine cancer noted in many countries cannot be explained only by an increase in average life expectancy - it is also associated with the progressive growth of diseases of civilization.

The incidence of endometrial cancer (EC) has doubled in some regions over the past 10 years, and in terms of incidence, this tumor ranks 1st among all malignant tumors of the female genitalia (N.P. Napalkov et al., 1983; Ya.V. Bokhman. , 1989; Chissov V.I., 2004).

The widespread use of methods for early detection and in-depth diagnosis of endometrial cancer, radiation and drug treatment dictate the need for periodic revision of the principles and methods of therapy.

Currently, surgical methods, radiation and combined treatment, as well as hormonal therapy are used as standard. For relapses and metastases of uterine cancer, the treatment of choice is chemotherapy based on platinum, fluorouracil, and taxa.

There are very few reports in the modern literature on the use of chemoradiation treatment in patients with primary endometrial cancer. All of them relate to postoperative irradiation and the introduction of cytostatics, in order to reduce the risk of relapse of the disease.

Chen ZY, Ma YB et all. (2007), using a combination of postoperative radiation and chemotherapy with the drugs: carboplatin and taxol, achieved an increase in the relapse-free interval by 46% in patients with uterine cancer with morphologically verified metastases to regional lymph nodes.

Analysis of the immediate results of treatment of patients with stage III-IV endometrial cancer who received radiation therapy, chemotherapy alone and a combination of radiation and chemotherapy showed effectiveness in the group with chemo-radiation therapy: the frequency of immediate clinical effects was 70, 59 and 79%, respectively Alvarez Secord A., Havrilesky LJ, et all (2007). The research will continue.

In turn, Deeks E (2007) did not reveal the advantages of combining postoperative irradiation of patients with parallel administration of chemotherapy drugs (carboplatin, Taxol), while the toxicity index was unreasonably high.

Conclusion

Evaluating the methods of treating common processes of cervical cancer, we can come to the conclusion that the main method of treatment is radiation therapy, as an independent method and as a component of combined treatment.

The undeniable advantage of combining radiation treatment with chemotherapy has been proven. The standard today can be considered the weekly administration of platinum drugs during radiation treatment, as well as the use of fluoropyrimidine derivatives as radiomodifying agents.

The question of chemoradiation treatment of endometrial cancer remains open, and all of the above only confirms the need for further research in this direction and, possibly, the development of not only new regimens for the administration of cytostatics in combination with radiation therapy in patients with endometrial cancer, but also the synthesis of fundamentally new drugs.

S.Ya. Maksimov, K.D. Guseinov, SB. Baranov, 2008 BBK P569.714-50
Federal State Institution “Research Institute of Oncology named after. N.N. Petrova Rosmedtekhnologii", St. Petersburg

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In the structure of human malignant tumors, head and neck cancer accounts for about 6%. About 60% of cases are upper respiratory tract cancer in stages III-IV. Abandoned stages of cancer, which appear during the initial treatment of patients, are difficult to treat, and the survival rate of patients is low.

In most such cases, surgical removal of the tumor is impossible or is associated with significant removal of tissue from the head and neck, which leads to disability of the patient. One of the main methods of treatment for advanced tumors of this localization is chemoradiotherapy. Treatment of these patients with one antitumor method (surgical or radiation) gives worse results than combination therapy.

The key to a significant improvement in the quality of treatment for cancer patients is the use of modern anticancer drugs. Chemotherapy (CT), according to treatment protocols, is prescribed in the following regimens:

- neoadjuvant chemotherapy followed by surgery or radiation therapy;

Combined chemotherapy (carried out simultaneously with radiation treatment);

Adjuvant chemotherapy (after surgery or radiation therapy).

Neoadjuvant chemotherapy reduces tumor mass and thus makes it possible to reduce the volume of surgical intervention and promotes more effective tumor regression during the next irradiation. In this case, it is possible to identify the sensitivity of the tumor to chemotherapy and, if the result is satisfactory, they can be prescribed after surgery and radiation therapy in the adjuvant mode. Neoadjuvant chemotherapy is prescribed from 2 to 6 cycles with an interval of 3-4 weeks.

The simultaneous (combined) use of chemotherapy and radiation therapy helps to reduce the incidence of local relapses and metastases.

The administration of chemotherapy drugs during radiation therapy enhances the therapeutic effect and, according to some authors, can be considered an alternative to surgery. In addition, chemoradiotherapy for unresectable tumors promotes regression of tumor tissue. In such cases, surgical removal becomes possible.

Monitoring and improving the quality of treatment is possible by determining the morphological changes in tumors that occur under the influence of antitumor therapy (therapeutic pathomorphosis), which makes it possible to identify the effectiveness of the treatment and the need for further treatment.

So, treatment of patients with stage III-IV upper respiratory tract cancer using chemoradiotherapy, both in the form of neoadjuvant chemotherapy with telegammatherapy (TGT), and with combined chemotherapy with THT, is quite effective. Both chemoradiation treatment regimens for these patients provide a good objective tumor response to therapy, and the percentage of complete tumor regression is observed in almost half of the patients. However, combined chemotherapy with THT has less impact on the quality of life of patients, and their overall three-year survival rate was significantly higher.

1) severe general condition of the patient;

2) pregnancy;

3) tumor damage to neighboring organs (bladder, rectum);

4) uterine fibroids, ovarian tumors;

5) purulent inflammatory processes in the pelvis;

6) distant metastases;

7) pyelo- and glomerulonephritis;

8) severe forms of diabetes mellitus;

9) atresia and stenosis of the vagina, preventing intracavitary gamma therapy

Chemoradiation therapy

cancer uterus radial cervix

The main role in the treatment of patients with cervical cancer (CC) is played by surgery and radiation therapy. Surgery is the mainstay of treatment in the early stages of the disease (IA-IB), while radiation therapy, alone or in combination with surgery, is widely used in the treatment of locally advanced cervical cancer (IV2-IVA). The 5-year survival rate when using radiation therapy reaches 65% and varies from 15% to 80% depending on the extent of the tumor process. Progression of the process in the pelvic area is the most common cause of death in patients with advanced cervical cancer. Although radiation therapy using increased doses of radiation leads to a decrease in the incidence of local progression, radiation damage to tissues and pelvic organs limits the possibility of further increasing the dose. In addition, radiation therapy does not effectively control metastases in the paraortic retroperitoneal lymph nodes, which are observed in 30% of patients with a locally advanced process, and does not affect the growth of distant metastases.

All this was a prerequisite for the combined use of radiation therapy and chemotherapy in the treatment of patients with cervical cancer. This approach has a number of theoretical justifications. Antitumor drugs increase radiation damage to tumor cells by disrupting the repair mechanism of damaged DNA, synchronizing the entry of tumor cells into phases of the cell cycle that are most sensitive to radiation damage, reducing the number of tumor cells in the resting phase, and the ability to kill radiation-resistant tumor cells that are in a state of hypoxia. In addition, the antitumor drugs themselves have a cytostatic effect not only against the primary tumor and regional metastases, but are also able to control existing distant metastases. Thus, the combined use of radiation therapy and chemotherapy should increase the antitumor effect of treatment in patients with cervical cancer.

The use of chemotherapy and radiation therapy can be sequential, when one method is used first and then the other, or two methods are prescribed simultaneously. The sequential use of radiation therapy at the first stage and drug therapy at the second stage seems unpromising due to pronounced fibrotic changes in the irradiation zone and mechanical difficulty in getting antitumor drugs into the tumor growth zone. The most commonly used sequence is chemotherapy (neoadjuvant) followed by radiation therapy. In addition to the above theoretical premises, chemotherapy at the first stage should reduce the size of the primary tumor and facilitate radiation therapy.

In 6 studies, more than 1800 patients with cervical cancer received chemoradiotherapy. 5 studies noted a 30-50% reduction in the risk of death from cervical cancer when using chemoradiotherapy compared with radiation therapy. The summation of the treatment results of all 1800 patients in 6 studies indicates a significant reduction in the risk of death from CC by 36% in the chemoradiotherapy group.

Thus, the presented data indicate the advisability of combined radiation therapy and chemotherapy in patients with locally advanced cervical cancer. It is difficult to say which chemotherapy regimen should be recommended.

It is likely that at different stages of the disease, the addition of chemotherapy should pursue different goals. If in the early stages chemotherapy should primarily potentiate the local effect of radiation therapy, then in later stages of the disease the purpose of chemotherapy is to suppress distant metastasis. Hence the difference both in the choice of cytostatics and in the intensity of chemotherapy.

The invention relates to medicine, in particular to oncology, and concerns the correction of hematopoietic depression caused by chemoradiotherapy. For this, it is proposed to use sodium nucleospermate obtained from the milt of sturgeon fish in doses of 15 - 225.0 mg. 2 salary f-ly, 2 ill., 6 tables.

The invention relates to medicine, namely to oncology, and concerns methods for correcting the side effects of chemoradiotherapy in cancer patients. One of the most dangerous complications of chemoradiotherapy is depression of hematopoiesis, which occurs when even therapeutic doses of cytostatics are prescribed. This complication not only makes it impossible to continue an adequate course of chemotherapy, but also increases the risk of developing bacterial infections, and sometimes leads to death. The arsenal of methods for correcting the side effects of chemoradiotherapy is quite diverse. They use bone marrow transplantation, the introduction of leukomass, colony-stimulating factors, as well as pharmacological drugs - pentoxyl, zymosan, vitamins of various groups. However, bone marrow transplantation involves additional traumatic intervention, and the introduction of leukomass can cause an immune conflict. At the same time, drug therapy is not effective enough. There is a known method for correcting the side effects of chemoradiation therapy, including the administration of sodium nucleinate (salt of nucleic acids obtained by hydrolysis of yeast) in the form of a 2-5% solution, 5-10 ml intramuscular, 1-2 times a day for 10 days or more. However, sodium nucleinate injections are extremely painful and have little effectiveness. At the same time, numerous studies in this direction of deoxyribonucleic acid and its salts are still at the preclinical level. The essence of the invention is that the claimed method uses the drug sodium nucleospermate in doses of 15-225 mg. Before administration, the drug is heated to 37 o C, and administration is carried out subcutaneously, slowly, and in case of “acute” leukopenia, the drug is administered from the second day of using a loading dose of cytostatics, for example, according to the CAM regimen, and administration is carried out within 1-10 days. For “chronic” leukopenia, the drug is administered after a course of chemotherapy, once, or over 3-8 days. The sodium nucleospermate preparation is a mixture of sodium salts of polychlorohydrates of derivatives of deoxyribonucleic and ribonucleic acids from sturgeon sperm with a nucleic acid content in terms of Na-DNA from 90 to 105% with a nitrogen to phosphorus ratio from 1.3 to 1.8 and 1.8 M.M. 66000-400000 D. “Chronic” leukopenia means leukopenia caused by various agents (chemotherapy, radiation therapy, chemoradiation therapy), existing in the patient for 2 - 4 weeks without a tendency to spontaneous recovery. By “acute” leukopenia we mean leukopenia caused by the administration of loading doses of cytostatics, with a known time frame for the development and recovery of deep leukopenia. To disclose the essence of the invention, the results of clinical studies of sodium nucleospermate in cancer patients with side effects from chemoradiotherapy are presented. The research was carried out at the Research Center of the Russian Academy of Medical Sciences, Moscow Scientific Research Institute named after. Herzen, Scientific Research Institute of Chemical Economy and others. A total of 71 patients with different tumor localizations (lung cancer, breast cancer, memphosarcoma, neuroblastoma) were studied. 1. Study of sodium nucleospermate in patients with chronic leukopenia. The study group included patients with different tumor localizations who developed chronic leukopenia. By the time of the planned next course of treatment, the level of leukocytes in the blood was below 2000 per 1 mm 3 of blood. Before starting sodium nucleospermate, two repeat blood tests were performed and if the white blood cell count remained below 2000, the drug was administered on the same day. Sodium nucleospermate was administered in a single dose of 75 mg (5 ml of a 1.5% solution) or in a single dose of 150 mg (10 ml of a 1.5% solution) once or over 3-8 days. Before administration, the bottle with the drug was heated to 37 o C, after which the contents of the bottle were administered to the patients subcutaneously for 1 minute. The effectiveness of the drug was assessed by blood tests (leukocytes) on days 1, 3, 5 and 7, as well as a myelogram on days 6-7 after administration of the drug. During the study period, patients did not receive additional hemostimulants, vitamins, corticosteroids or blood transfusions. The research results showed that when using sodium nucleospermate, it was possible to restore the number of peripheral blood leukocytes to 3000 or more in 87% of patients. Recovery of the number of leukocytes was observed on average at 6.3 days. It is characteristic that the increase in the number of leukocytes in the peripheral blood was accompanied by an increase in the content of myelokaryocytes in the bone marrow aspirate by an average of 3.7 times. In all cases, after administration of the drug according to the claimed method, chemotherapy was continued in the planned doses. In all cases, there was no further decrease in the number of leukocytes during chemotherapy. The effectiveness of using sodium nucleospermate in patients with chronic leukopenia is illustrated in Table. 1. From the presented table. Table 1 shows that administration of the drug either once or over 3-8 days, 75-150 mg, causes a significant leukostimulating effect in cancer patients. 2. Study of sodium nucleospermate in patients with acute leukopenia. The study group included patients with “acute” leukopenia who received combination chemotherapy in the inverse mode according to the CAM regimen for small cell lung cancer. Before treatment, patients underwent a complete clinical examination (radiography of the lungs, CT scan of the liver, adrenal glands, brain, skeletal scan, biochemical blood test, myelogram). Patients with morphologically proven localized SCLC on the first day of treatment received: cyclophosphamide 1.5 g/m2 IV; adriamycin 60 mg/m2 IV; methotrexate 30 mg/m2 i.v. Starting from the second day of treatment, patients were administered sodium nucleospermate subcutaneously in a single dose of 75 mg (5 ml of a 1.5% solution) or 150 mg (10 ml of a 1.5% solution). Before administration, the bottle with the drug was heated to 37 o C, after which the contents of the bottle were administered to the patients subcutaneously slowly over 1 minute. Administration of the drug was continued for 5 or 10 days. Blood tests were performed daily from days 2 to 20; On days 6–10, a control myelogram was performed. During the study period, patients did not receive other hemostimulants, vitamins, corticosteroids or blood transfusions. As a result of the research, the following was shown. Of the 14 patients who received sodium nucleospermate for 5 or 10 days, the drug was administered in a single dose of 75 mg to 5 patients (12 courses of chemotherapy), and in a single dose of 150 mg to 9 patients (22 courses of therapy). The results are presented in table. 2. As follows from the table, grade 3 leukopenia was detected in 41 (45%) patients, and grade 4 - in 58 (27%) patients. The use of the drug made it possible to carry out chemotherapy without leukopenia or with a slight decrease in the number of leukocytes to grade 1-2 in 20 (36%) patients. A comparison of the effectiveness of sodium nucleospermate depending on the size of a single dose revealed a slight increase in the hemostimulating effect when using a dose of 150 mg (Fig. 1). Profound leukopenia (grade 4) occurred when using a dose of 75 mg in 58% of patients, and when using a dose of 150 mg only in 27% (the differences are not statistically significant). The recovery time for blood counts in 14 patients with SCLC is presented in Table. 3. In patients who received the drug sodium nucleospermate in a single dose of 75 mg, the average recovery time of leukocytes, calculated from the start of drug administration, ranged from 17.2 days for 1 course to 15.8 - 16 days for 2 and 3 courses. In patients who received a single dose of 150 mg, these indicators were 15.8 - 16.3 - 11.0 days, respectively. The average recovery time for leukocytes, calculated from the end of the course of administration of the drug in the indicated doses, was 7.3 days in the 1st course to 5.8 - 6.0 in the 2nd - 3rd courses. The reduction in the recovery time of leukocytes by the 3rd course is apparently associated with the accumulation of the drug or with its cumulative effect on the bone marrow. Of the 14 patients, grade 3-4 leukopenia was observed in 12 patients, only 1 had grade 4 leukopenia. The duration of grade 3 leukopenia in patients who received sodium nucleospermate in a single dose of 150 mg for 10 days was reduced from 6 - 9 days in the 1st course to 3 - 6 days in the 2nd course (Fig. 2). The same indicator, obtained in a group of 19 patients receiving GM-CSF (data from the Chemotherapy Department of the Cancer Research Center, 1993), amounted to 4 - 10 days. In fig. Figure 2 shows the average number of leukocytes and neutrophils in the peripheral blood of patients with SCLC in a semi-logarithmic coordinate system. Curves demonstrating hematopoiesis indices during the use of sodium nucleospermate are shown in comparison with the number of neutrophils calculated for patients who did not receive hemostimulants after similar intensive chemotherapy for SCLC (“placebo”, n-108, Crawford et al., 1991). It can be seen that when using sodium nucleospermate, stimulation of leukocytes occurs due to neutrophils, which is not observed in the “placebo” group. Stimulation is expressed in a decrease in the depth of leuko- and neutropenia by 2 - 2.5 times; absence of leukopenia of the 3rd - 4th degree and neutropenia of the 4th degree; reducing the duration of grade 3 neutropenia from 7 to 5 days. In table Figure 4 shows a comparative characteristic of hematopoietic restoration in patients with intensive chemotherapy without the use of hemostimulants (placebo) with sodium nucleospermate and with G-CSF. As follows from the data presented, in the placebo group, grade 3 neutropenia lasted from 7 to 11 days, while with the use of nucleospermate it was reduced to 5 - 9 days, and with G-CSF to 3 - 4 days. Grade 4 neutropenia in the placebo group lasted 4-5 days, with sodium nucleospermate - 1 day, and with G-CSF - 2 days. Maximum neutropenia in the placebo group reached 100 cells, with sodium nucleospermate - 300 cells and with G-CSF - 400 cells. The period of onset of maximum neutropenia was the same in all comparison groups and was equal to 10 days. The first day of restoration of neutrophils to 1000 cells was, respectively, 21-14-15, and to 2000 cells, respectively, 20-15-12. When analyzing the effectiveness of sodium nucleospermate in patients after the 1st course of chemotherapy, the following results were noted (Table. 5). The number of patients in whom the number of leukocytes reached 3000 cells and neutrophils 2000 cells by days 14–17 was 11 people (85%). The number of patients who could undergo the 2nd course of treatment on days 14–17 was 8 people (62%). A study of myelograms in 9 patients showed (Table 6) that the indicators of bone marrow hematopoiesis in all patients before the start of chemotherapy were within normal limits. After chemotherapy against the background of sodium nucleospermate, 6 patients noted a “decrease in myelokaryocytes due to myelocytes and promyelocytes by 15–40%, and in three patients on days 9–12 there was a significant increase in young forms of granulocytopoiesis (promyelocytes and myelocytes) and a corresponding increase in the neutrophil maturation index from 0.8 to 5.7 - 18.0. The relative number of lymphocytes increased by 10 - 37%, while the number of erythroid cells remained unchanged. It is obvious that the use of sodium nucleospermate in 14 patients with SCLC during intensive chemotherapy made it possible to reduce the depth of leuko- and neutropenia, shorten their duration, conduct chemotherapy without septic complications, and in 63% of patients begin repeated courses of chemotherapy at intervals of 14 - 17 days. Thus, a clinical study of sodium nucleospermate in cancer patients allowed us to draw the following conclusions. 1. Sodium nucleospermate in patients with chronic leukopenia restores the leukocyte composition of peripheral blood (efficacy 87%). 2. In parallel, there is an increase in the number of myelokaryocytes in the bone marrow aspirate (3.7 times). 3. The use of sodium nucleospermate allows not only to restore hematopoiesis, but also to continue chemotherapy as planned. 4. The use of sodium nucleospermate in patients with acute leukopenia during intensive chemotherapy has a hemostimulating effect and helps prevent the development of deep leukopenia and neutropenia and associated septic conditions. The hemostimulating effect of sodium nucleospermate is associated with stimulation of granulocytopoiesis (promyelocytes and myelocytes), which is manifested in an increase in the neutrophil maturation index by more than 7 times. An example illustrating the essence of the invention. Patient Bykov I.A., born in 1939 Outpatient card N 94/5157. Diagnosis: lymphosarcoma of all groups of peripheral lymph nodes, retroperitoneal lymph nodes of the liver, spleen with leukemia of the type of prolymphocytic leukemia, IV Ast. Histological conclusion: N 225/94 dated 13. 01.94 Lymphosarcoma from cells of the prolymphocyte type. 02.16 - 03.01.94 - 1st course of therapy according to the CIPP regimen (leukeran 10 mg per. os, vinblastine 10 mg intravenously on days 1.8, natulan 150 mg per. os 1 - 14 days, prednisolone 60 mg /day 1 - 14 days. The 2nd course of chemotherapy was not started due to leukopenia 01/IV - 50000, 04/IV - 38000. 04/04/94, sodium nucleospermate was administered, in accordance with the study protocol. Blood test results : 04/06 platelets - 48000, 04/08 platelets - 52000. Thus, the claimed method for correcting the side effects of chemotherapy has the following advantages compared to the known ones: 1. Effectively restores the leukocyte composition of peripheral blood in acute and chronic leukopenia. 2. Stimulates bone marrow hematopoiesis. 3. Allows you to continue adequate chemotherapy as planned. 4. Reduces the risk and frequency of infectious complications. 5. Does not have a negative effect on the body. All of the above indicates the possibility of widespread use of the claimed method in clinical practice. Literature 1. Belous A.M. Exogenous nucleic acids and restoration processes.-M.: Medicine, 1974, p. 126 - 140. 2. Gershanovich M. L. Complications during chemotherapy and hormonal therapy of malignant tumors. - M.: Medicine 1974, p. 126 - 140. 3. Loginov A.S. and others. Reparative effect of nucleic acid preparations in experimental gastric ulcers. Bulletin exp. biol. and med., N 7, 1991. 4. Mashkovsky M.D. Medicines.-M.: Medicine, vol. 2, 1985. 5. Rychnev V.E. Nucleic acids and their therapeutic applications. Medical Affairs, N 8, 1981, p. 114 - 118. 6. Slinchak S.M. Oncology. - Kyiv, Vishcha school, 1989, p. 199 - 204. 7. Bregni M, S. Siena Breakthrough in cytokine therapy: an overview of GM-CSF. Royal Society of Medicine Services Int.Congress and Symposium Series 1992, N 170, p. 1 - 6. 8. P. Gupta et al. Bone Marrow Transplantation, 1992, N 9, p. 491 - 492. 9. P. Riikonen, V. Saarinen. Medical and Pediatric Oncology, 1992, N 20, p. 489 - 496.

Claim

1. A method for correcting depression of bleeding caused by chemoradiotherapy, including the injection of nucleic acid derivatives obtained from the milt of sturgeon fish, characterized in that the drug sodium nucleospermate is used, which is a mixture of sodium salts of polychlorohydrates of derivatives of deoxyribonucleic and ribonucleic acids with the content of nucleic acids in terms of on Na-DNA 90 - 105% with a nitrogen to phosphorus ratio from 1.3 to 1.8 and 1.8, M.M. 66000-400000 D, in doses of 15 - 225.0 mg, and the drug is heated before administration, and administration is carried out subcutaneously slowly. 2. The method according to claim 1, characterized in that in case of acute leukopenia the drug is administered from the second day of using cytostatics according to the CAM regimen for 1 to 10 days. 3. The method according to claim 2, characterized in that in case of chronic leukopenia, administration is carried out after a course of chemotherapy once or over 3 to 8 days.

The invention relates to imidazolidyl macrolides (substances with a macrocyclic lactone ring), which are useful for mammals in the treatment of autoimmune diseases (such as juvenile or new-onset diabetes mellitus, multiple sclerosis and rheumatoid arthritis, liver disease, inflammation of the choroid, allergic encephalomyelitis and glomerulonephritis), immunosuppression, treatment of infectious diseases and/or prevention of foreign organ rejection in transplantation (eg, transplants, including xenografts, bone marrow, kidney, liver, heart, skin, small intestine and pancreatic islet cells), with local treatment of skin diseases associated with inflammation or increased cell proliferation, and skin manifestations of immunostimulated diseases (such as psoriasis, diffuse neurodermatitis, contact dermatitis and other eczematous dermatitis, seborrheic eczema, lichen planus, pemphigus vulgaris, pemphigoid pemphigoid, congenital epidermolysis bullosa, urticaria, angioedema, vasculitis, erythema, cutaneous zosinphilic leukocytosis, lupus erythematosus or alopecia areata), male islet alopecia, senile alopecia, in the treatment of diseases associated with reversible obstruction of the airways, in particular asthma, inflammation of the mucous membrane and blood vessels and infections caused by the cytomegaly virus, with the immunity of microorganisms to the action of drugs, idiopathic thrombocytopenic purpura, chronic recurrent aphthous stomatitis (Behçet's disease), conjunctivitis, granulomatous disease (Crohn's disease), corrosive corneal ulcer (Moraine), inflammation of the choroid of the eyeball, acute intraocular inflammation and/or liver damage caused by ischemia

The invention relates to new N-substituted -3-(2",3"-dihydroxypent-2"-yl)-7-[(2,6-dideoxy-3-C-methyl-3-O--L-ribo- hexapyranosyl)-oxy]-9-[(3,4,6-trideoxy-3-amino-B-D-xylo-hexapyranosyl)-oxy]-2,6,8,10,12-pentamethyl-4,13-dioxabicyclo - tridec-12-en-5-one-compounds with motilinagonistic properties, their acid addition salts, as well as pharmaceuticals containing these compounds and methods, as well as intermediate products for their preparation

Chemotherapy can reduce the ability of tumor cells to repair radiation-induced DNA damage. Many of the commonly used chemotherapy drugs with significant activity against esophageal and gastric cancer are radiosensitizers (fluorouracil, cisplatin, mitomycin, taxane). There is reliable evidence that the incidence of POP is significantly higher with chemoradiation therapy than with radiation and chemotherapy prescribed separately. There is significant appeal in achieving enhanced local therapy combined with systemic benefits, as appears to be the case with the standalone use of preoperative chemotherapy. When complementary to surgical treatment, it is not clear that CR is necessarily the only useful endpoint. Preoperative chemoradiation therapy has the added benefit of providing direct data to guide the development process and optimize the chemotherapy-radiotherapy combination regimen for use as definitive treatment.

Radiation and chemotherapy rely on an acceptable balance between increasing the tumor response rate, on the one hand, and damage to intact tissue in combination with patient tolerance, on the other. While many of the side effects of chemotherapy appear relatively early (eg, hair loss, vomiting, and myelosuppression), the side effects of radiation therapy may appear later, 6 months to a year after treatment. If radical surgical treatment is supplemented with combination therapy, the potentially high complication rate becomes significant.

Efficacy of chemoradiotherapy

Non-randomized studies of chemoradiotherapy have been described in the literature since the second half of the 1980s. Review of articles by Geha et al. summarizes 46 studies including 20 patients or more. Overall, the pooled data from these studies show that of 2704 patients, 79% were operated on, with a POP rate of 24% of those treated and 32% of those treated with resection. According to histology, 68% of these patients had squamous cell carcinoma, and 32% had adenocarcinoma.

With the accumulation of experience in using this method of treatment, certain conclusions will be drawn. Attempts to increase the radiation dose may result in unacceptable complication rates, especially when using a high dose per procedure. The published incidence of CRT-related deaths in non-randomized studies is 0-15% (mean 3%). Postoperative mortality ranges from 0-29% (average 9%). Adult respiratory distress syndrome, anastomotic leak and breakdown, pneumonia and sepsis were the most common causes of death after esophagectomy. Treatment-related deaths account for 3-25% (average 9%) of all patients treated. It seems clear that the risk of chemotherapy-related toxicity, especially myelosuppression, increases with the number of drugs used and the intensity of the chemoradiotherapy regimen. An increased risk of tracheobronchial fistula has been reported. However, most of the published studies did not use complex radiation therapy techniques, which allows for greater precision and preservation of key portions of intact tissue.

Grades of response to CRT are described by Mandard et al. Five grades of response (ranging from no identifiable tumor to no regression) provide a more objective approach to the problem. In this article, the significant predictor of disease-free survival after multivariate analysis was the degree of tumor regression. There is evidence that POP represents a survival advantage compared with patients who do not achieve POP.

In three studies chemotherapy was given sequentially with radiotherapy and in four studies it was given simultaneously. Two studies used sequential treatment for squamous cell carcinoma, administered at relatively low doses of radiation therapy, and showed no convincing evidence of a survival benefit with combination therapy. In a large study by the European Organization for Research and Treatment of Cancer (EORTC), which included 282 patients, cisplatin chemotherapy was administered in close sequence with radiation therapy. Radiation therapy was administered in an intermittent course and at a relatively high dose per procedure (2 courses with a radiation dose of 18.5 Gy for 5 daily appointments, 2 weeks apart). Patients receiving chemoradiotherapy were more likely to have curative resection. Relapse-free survival was significantly longer (3-year CRT+X 40% versus X 28%). There was no difference in overall survival, largely due to significantly higher postoperative mortality in the CRT group (12% versus 4%). Apinop et al. reported a study of synchronous chemoradiotherapy in 69 patients with histologically confirmed squamous cell carcinoma without improvement in survival.

There are three large studies of preoperative concurrent chemoradiotherapy.

Walsh's research has influenced practice changes, especially in the United States. To 113 patients with adenocarcinoma, cisplatin and fluorouracil were prescribed with radiation therapy (40 Gy) for 3 weeks. There was an advantage in overall survival due to the CRT group (average 16 months compared with 11 months; 3-year survival rate 32% compared with 6%). The complication rate in this study was negligible. The radiotherapy technique and fractionation may explain this. However, the question arises: why was survival particularly poor in the surgery-only group? Basic staging standards may possibly lead to an imbalance in true staging within the treatment group. The University of Michigan study randomized 100 patients with squamous cell carcinoma and adenocarcinoma. Surgical treatment consisted of transhiatal resection. Patients in the chemoradiation group received 45 Gy for 30 treatments with cisplatin, fluorouracil, and vinblastine. At the first analysis, there was no significant difference between the groups, but by year 3 there was a statistically significant benefit of combination therapy, with overall survival of 32% versus 15%. The final analysis showed no survival benefit and demonstrated the dangers of early publication of a study that has essentially little evidence.

The results of the Australasian Gastro-Intestinal Trials Group (AGITG) study were criticized for the low dose of radiotherapy and only one cycle of chemotherapy with cisplatin and fluorouracil. Although the study was generally negative, there is some information about the direction of future approaches. There was a significant difference in survival in patients with squamous cell carcinoma on histological examination (36% overall) with additional chemoradiotherapy and a much higher rate of pathological complete response. It is necessary not only to conduct the study, but also to pay attention to the quality of all components of treatment and staging to ensure that the results of past studies are not repeated. One such study has unfortunately been discontinued in the US (NCCTG-C9781). The results of the intergroup study INT-0116 (SWOG 9008) were presented at the meeting of the American Society of Clinical Oncology in 2000. While this was a study primarily of postoperative chemoradiotherapy for gastric cancer, it included tumors of the esophagogastric junction. It was felt that the positive results of the SWOG 9008 trial would be offset by additional randomization in the study with a surgical control group. Additional recruitment was already poor due to preoperative chemoradiotherapy, which had become the accepted standard of care in the United States. There are still major unanswered questions, but the surgery-only arm is unlikely to be considered for use in the UK following the results of the OEO2 chemotherapy trial. There is a correct clear distinction in future studies between adenocarcinoma and squamous cell carcinoma. As there has been a trend toward treating squamous cell carcinoma with primary chemoradiotherapy, the role of preoperative CRT may be reconsidered as a means of improving outcome for patients with adenocarcinoma that may still be predicted by negative prognostic features (eg, predicted positive circumferential margin) as a philosophy treatment of rectal cancer. For this selected group, increased toxicity may be warranted.

At present, preoperative chemoradiotherapy should only be considered in the context of clinical trials.

One problem is the poor quality of validity of older studies, as subgroup analyzes are of limited value. For some other diseases, separate treatment and research approaches are still widely used. In the future, there is a need to move toward selecting patients for specific treatment pathways based on molecular pathology and staging information.

The current approach in the UK is to provide more precise preoperative chemotherapy than chemotherapy, particularly for adenocarcinoma. Any additional benefit from additional radiation therapy to chemotherapy is offset by increased morbidity and postoperative mortality. In the United States, there remains increased interest in optimizing chemoradiotherapy regimens with various drug combinations, especially by reducing morbidity and mortality through the use of new technologies. For squamous cell carcinoma, the emphasis is on developing pathways for chemoradiotherapy as definitive treatment.

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Side effects from chemotherapy

Treatment of cancer includes a course of chemotherapy treatment. This method is used mainly in advanced stages of the cancer process, when distant metastases have spread through the lymphatic and circulatory systems. Chemotherapy involves the intravenous administration of powerful anticancer drugs. Their action is aimed at destroying pathological cells, but the peculiarity and danger is that these drugs do not distinguish between malignant tissues and healthy ones. The patient's condition worsens greatly after a course of chemotherapy, but the cancer cells are also partially destroyed.

Chemotherapy drugs cannot destroy healthy cells equally quickly as pathological ones, and this allows their use. The bottom line is that atypical cells divide much faster, and chemotherapy drugs affect them specifically. Healthy cells are less affected, and this is due to their slow growth.

Treatment effectiveness and complications

The chemotherapy method of treatment is quite effective and makes it possible to influence not only the main focus of the malignant process, but also isolated metastases.

Healthy cells can recover after the action of drugs, unlike pathological ones, but not to the full extent. These are the side effects of chemotherapy.

Most complications after therapy disappear almost immediately, but the most dangerous and unpleasant side effects of chemotherapy remain and persist for many years.

The mildest (non-dangerous) side effects of chemotherapy for the body are hair loss, due to damage to the weakest cells in the body, the hair follicles. Also most at risk are the tissues of the feet and hands.

Severe side effects from chemotherapy:

• Chemotherapy treatment leads to the development of osteoporosis, when bone tissue weakens, becomes brittle and is subject to traumatic damage, with fractures and dislocations occurring very easily;
• leukemia is the most severe complication after treatment and occurs rarely while taking Cyclophosphamide;
• increased lacrimation - such side effects from chemotherapy are associated with the administration of a drug such as Adriamycin;
• the drug Tacoster, which is included in the course of treatment, provokes problems with the cardiovascular system after treatment, therefore they try to use it in minimal doses;
• after using drugs such as Abraxan and Taxanov, severe baldness develops, which is quite difficult to treat, and even after it, returns again.

Side effects from chemotherapy appear to varying degrees after the administration of drugs, and this depends on their strength, composition, form of cancer, and characteristics of the patient’s body. Let's look at the most common side effects of chemotherapy, which appear both during treatment and after therapy.

Dyspeptic disorders

Nausea, frequent vomiting, and intestinal disorders are the most common side effects of chemotherapy. This is due to the high susceptibility of stomach and intestinal cells to treatment drugs. They are most quickly exposed to negative effects after taking medications, but at the same time they also recover quickly. Some patients are not even aware of these manifestations, while others suffer from them every day and even after therapy.

The manifestation of dyspeptic symptoms is greatly influenced by the emotional state of patients; anxiety after diagnosis and the need to carry out chemotherapy leads to frustration, and therefore patients are preliminarily prepared before treatment. Nausea can be caused by many factors, for example, after taking certain sedatives and painkillers. Also, constipation, gastrointestinal disorders, and the inability to eat normally lead to constant nausea and vomiting.

It is important to carry out corrective therapy aimed at reducing emotional stress and relieving nausea before starting treatment. Side effects during chemotherapy can become a contraindication for treatment in people with a weakened body, in the presence of infectious diseases and chronic blood diseases. The main method of combating minor negative effects of treatment is targeted drug therapy to relieve the main symptoms.

Hair loss

Side effects from chemotherapy are associated with disruption of the functioning of healthy cells in the body. Hair follicles are most susceptible to negative effects, and therefore very often the adverse effects of drug administration affect the hair.

Strong medications destroy the cells from which hair grows, so baldness occurs not only on the head, but can also occur throughout the body. This side effect is otherwise called alopecia. Alopecia may appear within days or weeks of starting cancer treatment. Chemotherapy, the side effects of which are focused only on hair loss, does not pose a danger to the patient, but, in turn, brings severe emotional discomfort.

In some situations, you can prevent hair loss by following these recommendations:

• individually select personal hygiene products based on natural plants that strengthen hair follicles;
• a short haircut will allow you to get used to the new look and it will become easier to deal with it after treatment;
• when your hair has fallen out, you need to take care of your scalp, wear a warm scarf at night, protect your head from wind and hot weather, and avoid drafts;
• In the summer, it is necessary to use sunscreen, which will prevent further damage to the skin on the head.

Anemia

Side effects of chemotherapy, such as anemic symptoms, are associated with disruption of red blood cells. Tissues are fed with oxygen from red blood cells, and a decrease in their number leads to a lack of oxygen, and this is manifested by anemic syndrome. In parallel with this, shortness of breath, constant weakness, pale skin, and chronic fatigue occur.

Such side effects require immediate treatment. If symptoms such as dizziness, rapid heartbeat, shortness of breath and general weakness appear, you should immediately consult a doctor to begin appropriate therapy.

• prolonged sleep of at least 7 hours will save more energy and reduce the adverse effects of oncology treatment;
• daily walks in the fresh air will fill the body with oxygen;
• you need to conserve your strength and do only the most necessary work during treatment;
• proper nutrition.

Appetite disturbance

Loss of appetite and weight loss are side effects that not only affect your physical condition, but also depress you mentally. Therefore, it is necessary to correctly create a diet and follow it for the entire period of treatment and after it. An important point is to drink enough fluid, which will normalize water balance, avoid exhaustion and improve appetite.

Any side effects can affect the appetite, some patients even refuse to eat food, while others experience an aversion to certain foods. To avoid this, you need to eat healthy foods every day, then monitor changes in the body, adjust the diet and create it yourself based on observations of your condition. Most often, this is not done by the patient himself, but by a nutritionist together with an oncologist, based on the medications used and the general condition of the patient.

It is necessary to eat at the same time during treatment and after a course of chemotherapy, so that the body gets used to it and does not reject food at the prescribed time. It is also better to eat food often, but in small portions, and the food should be varied, high-calorie, fresh and healthy.

You need to keep a special food diary in which you indicate all the foods and their quantities that are consumed during the day. This will help to monitor various problems in the body and correctly create a special permanent diet. If the condition is impaired, the recorded information will help determine which foods should be eliminated from your diet.

Skin and nail color

Drug treatment has a negative effect on the condition of the nails and skin; after the administration of potent drugs there is a risk of allergic reactions, but this is the least that can happen in the body. After treatment, patients often develop hives, various rashes, and purulent wounds on the body.

The skin becomes dry or, on the contrary, sweating increases, some areas of the body begin to itch and this can lead to skin irritation and secondary infection.

All processes of internal organs are visible on the skin, which means that any disorder can be determined by changes in complexion, the presence of ulcers or other manifestations on it.

Memory impairment

In patients after chemotherapy treatment, memory and thought processes are very often impaired. This is due to the negative effect of some antitumor drugs on brain cells. After treatment, patients find it difficult to solve ordinary problems, cannot get their act together and think about a question for a long time. In this case, all knowledge is preserved, but there is a certain inhibition, an inability to quickly reproduce the answer. It is very difficult for such patients to concentrate on anything; they forget phone numbers and names.

If symptoms such as constant melancholy, cloudy consciousness, heaviness in the head, difficulty in remembering appear, you must inform your doctor about this to change treatment.

Edema

A common consequence of cancer treatment is swelling, which can be associated with lymph obstruction, circulatory disorders, and a sedentary lifestyle. Some forms of cancer require surgical removal of not only the pathological focus, but also regional lymph nodes. Removal of nodes leads to stagnation of fluid, it accumulates in the lower extremities, arms, and even lungs.

Pulmonary edema is considered the most dangerous, since fluid is not released back from the lungs on its own, and this can be fatal.

Treatment of edema is carried out through surgical treatment - lymphatic drainage is performed. Diuretic drugs, physiotherapeutic methods, physical therapy are pre-prescribed, and nutrition is adjusted.

Each side effect affects the body to varying degrees, some go away without a trace, while others permanently change the state of health.

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Types of chemotherapy

1. 2. Classification
2. 3. How are chemotherapy drugs administered?
3. 4. How are dosages selected?

What is chemotherapy? How does it work? Main types of chemotherapy. Side effects and methods of dealing with them. How are treatment courses carried out? What are cycles?

Chemotherapy, along with surgery and radiation therapy, is one of the classic three treatments for cancer.

How do chemotherapy drugs work?

Cancer cells differ from healthy cells in their ability to divide uncontrollably. There are different groups of chemotherapy drugs with different mechanisms of action, but the essence of their work always comes down to the fact that they affect rapidly multiplying cells - not only cancerous ones, but also healthy ones, so chemotherapy is often characterized by serious side effects.

All chemotherapy drugs are divided into two large groups. Cytostatics (cytostatics) stop cell division. Cancer cells cannot reproduce; a mechanism of programmed cell death, apoptosis, is triggered in them. Cytotoxic drugs directly cause the death of tumor cells.

Chemotherapy is prescribed by an oncologist or a more highly specialized doctor - a chemotherapist. The choice of drugs depends on several factors:

• Type of cancer and its molecular genetic characteristics. Different tumors are sensitive to different drugs.
• Stage of cancer.
• Types of treatments that have been used before.
• Age and general health of the patient.
• Presence of concomitant diseases.

Monotherapy with one drug can be prescribed, but the best effect is usually achieved when the patient receives a combination of chemotherapy drugs with different mechanisms of action. Chemotherapy is often combined with other types of treatment.

Classification

The following main types of chemotherapy are distinguished:

• Neoadjuvant. Performed before surgery. In this case, its main goal is to reduce the size of the tumor so that it is easier for the surgeon to remove it.
• Adjuvant. Performed after surgical treatment. The tumor was removed, but cancer cells could remain in the patient's body. Chemotherapy helps destroy them and prevent relapse.
• As the main type of treatment. Chemotherapy may become the mainstay of cancer treatment when surgery is contraindicated or ineffective (in advanced stages).
• Chemoradiation therapy. A term that refers to a combination of chemotherapy and radiation therapy. This increases efficiency, but increases the risk of side effects.
• Chemoembolization. A specific type of treatment when an embolic drug in combination with a chemotherapy drug is injected into the artery feeding the tumor. Particles of the embolic drug block the lumen of the blood vessels, depriving the tumor of oxygen and nutrients, and the chemotherapy drug attacks the cancer cells.

Chemotherapy is used for both radical (with the goal of completely destroying the tumor and inducing remission) and palliative (reducing the size of the tumor, combating symptoms, prolonging the patient’s life) treatment.

How are chemotherapy drugs administered?

Most often, chemotherapy drugs are administered as solutions intravenously, through a needle, catheter, or implantable port systems. Sometimes they are taken in tablet form. This type of chemotherapy is called systemic because the drug enters the systemic bloodstream and is carried throughout the body.

In some cases, local chemotherapy is performed: the drug is injected directly into the place where the tumor is located:

• Intra-arterial - into the artery feeding the tumor.
• Into the abdominal cavity.
• Into the pleural cavity.
• Under the membranes of the brain and spinal cord.
• In the ventricles of the brain.
• Into the bladder.
• There are preparations for rubbing into the skin.

Local administration of the drug helps prevent its effects on healthy organs and avoid serious side effects.

How are dosages selected?

Correct selection of doses of chemotherapy drugs is a responsible task. If the dosage is too small, it will reduce the chances of successful treatment, and if it is too high, the risk of severe side effects will greatly increase. The corridor between effectiveness and safety, in which a chemotherapy doctor has to maneuver, is often very narrow.

There are two main methods for calculating chemotherapy doses: by the patient’s weight and by his body area. For certain groups of cancer patients, dosages must be selected individually:

• Aged people.
• Patients who have malnutrition are in a state of exhaustion.
• Patients who are overweight or obese.
• Patients who have concomitant health problems and, in addition to chemotherapy, are forced to take other medications.
• People suffering from anemia, immunodeficiency conditions, bleeding disorders, kidney and liver diseases.
• Children.
• Patients in whom chemotherapy is combined with radiation therapy.

How long does the course of treatment last?

It is difficult to give a definite answer to this question. It's individual. Courses may vary in length. For some patients, one course of treatment is enough, others require several. This is primarily determined by the type and stage of cancer, its molecular genetic characteristics, the general health of the patient, the type of chemotherapy drugs that were decided to be used, and chemotherapy protocols.

What are chemotherapy cycles?

Since chemotherapy drugs indiscriminately attack all rapidly multiplying cells, they are all toxic to the body to one degree or another. Therefore, they cannot be administered continuously for a long time. The body needs breaks to recover.

Chemotherapy is given in cycles. The medicine is administered once, either for several days in a row, or for several days every other day, followed by a break. The length of the cycles varies. It is usually measured in weeks and amounts to 7, 14, 21, 28 days.

The course of treatment may include several cycles. The doctor chooses the optimal schedule for administering the drugs, which, on the one hand, helps to achieve maximum effectiveness, while at the same time ensuring a minimal risk of side effects.

What are chemotherapy protocols?

The correct selection of chemotherapy drugs, their combinations and doses is a difficult task. In order to effectively solve it, the experience of one doctor is not enough. Numerous studies involving thousands of patients have been conducted around the world, and their results have formed the basis of chemotherapy protocols. These documents detail all the nuances of prescribing chemotherapy for different types and stages of cancer.

Doctors in different countries may follow different chemotherapy protocols. Some of them are completely or partially outdated, others take into account the most modern advances in the field of oncology.

Of course, the classic medical principle - “treat the patient, not the disease” - does not disappear anywhere. When working within the framework of a particular protocol, the doctor must always take into account the individual characteristics of the patient. This kind of cancer treatment is called personalized.

What side effects do chemotherapy drugs have?

Due to the fact that chemotherapy drugs attack not only tumor cells, but also actively reproducing healthy cells, they have numerous side effects. The patient may experience:

• Pain in different parts of the body.
• Nausea and vomiting.
• Hair loss, nail changes.
• Loss of appetite and taste perversion.
• Diarrhea or constipation.
• Increased fatigue.

Chemotherapy can lead to changes in the blood: increased bleeding, anemia, decreased immunity, and the risk of infectious complications increases. Different combinations of chemotherapy drugs are toxic to varying degrees.

Can the side effects of chemotherapy be managed? There are some effective ways:

• First of all, the doctor will give some recommendations about lifestyle and nutrition.
• To protect hair and nails during the administration of drugs, use cooling caps and special cooling bags for hands and feet.
• Maintenance therapy helps to cope with unpleasant symptoms and endure the course of chemotherapy more comfortably.
• If these measures do not help, you have to reduce the doses of chemotherapy drugs and replace them with safer ones. This may negatively affect the effectiveness of treatment.

1. 1. How do chemotherapy drugs work?
2. 2. Classification
3. 3. How are chemotherapy drugs administered?
4. 4. How are dosages selected?
5. 5. How long does the course of treatment last?
6. 6. What are chemotherapy cycles?
7. 7. What are chemotherapy protocols?
8. 8. What side effects do chemotherapy drugs have?

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Method for correcting side effects of chemoradiotherapy

The invention relates to medicine, in particular to oncology, and concerns the correction of hematopoietic depression caused by chemoradiotherapy. For this purpose, it is proposed to use sodium nucleospermate obtained from the milt of sturgeon fish in doses of 0 mg. 2 salary f-ly, 2 ill., 6 tables.

The invention relates to medicine, namely to oncology, and concerns methods for correcting the side effects of chemoradiotherapy in cancer patients.

One of the most dangerous complications of chemoradiotherapy is depression of hematopoiesis, which occurs when even therapeutic doses of cytostatics are prescribed. This complication not only makes it impossible to continue an adequate course of chemotherapy, but also increases the risk of developing bacterial infections, and sometimes leads to death.

The arsenal of methods for correcting the side effects of chemoradiotherapy is quite diverse. They use bone marrow transplantation, the introduction of leukomass, colony-stimulating factors, as well as pharmacological drugs - pentoxyl, zymosan, vitamins of various groups. However, bone marrow transplantation involves additional traumatic intervention, and the introduction of leukomass can cause an immune conflict. At the same time, drug therapy is not effective enough.

There is a known method for correcting the side effects of chemoradiation therapy, including the administration of sodium nucleinate (salt of nucleic acids obtained by hydrolysis of yeast) in the form of a 2-5% solution, 5-10 ml intramuscular, 1-2 times a day for 10 days or more. However, sodium nucleinate injections are extremely painful and have little effectiveness. At the same time, numerous studies in this direction of deoxyribonucleic acid and its salts are still at the preclinical level.

The essence of the invention is that in the claimed method the drug sodium nucleospermate is used in doses of mg. Before administration, the drug is heated to 37 o C, and administration is carried out subcutaneously, slowly, and in case of “acute” leukopenia, the drug is administered from the second day of using a loading dose of cytostatics, for example, according to the CAM regimen, and administration is carried out within 1-10 days.

For “chronic” leukopenia, the drug is administered after a course of chemotherapy, once, or over 3-8 days.

The sodium nucleospermate preparation is a mixture of sodium salts of polychlorohydrates of derivatives of deoxyribonucleic and ribonucleic acids from sturgeon sperm with a nucleic acid content in terms of Na-DNA from 90 to 105% with a nitrogen to phosphorus ratio from 1.3 to 1.8 and 1.8 M.M.000 D.

“Chronic” leukopenia means leukopenia caused by various agents (chemotherapy, radiation therapy, chemoradiotherapy) that exists in the patient for weeks without a tendency to spontaneous recovery.

“Acute” leukopenia means leukopenia caused by the administration of loading doses of cytostatics, with a known time frame for the development and recovery of deep leukopenia.

To disclose the essence of the invention, the results of clinical studies of sodium nucleospermate in cancer patients with side effects from chemoradiotherapy are presented. The research was carried out at the Research Center of the Russian Academy of Medical Sciences, Moscow Scientific Research Institute named after. Herzen, Scientific Research Institute of Chemical Economy and others. A total of 71 patients with different tumor localizations (lung cancer, breast cancer, memphosarcoma, neuroblastoma) were studied.

1. Study of sodium nucleospermate in patients with chronic leukopenia.

The study group included patients with different tumor localizations who developed chronic leukopenia. By the time of the planned next course of treatment, the level of leukocytes in the blood was below 2000 per 1 mm 3 of blood. Before starting sodium nucleospermate, two repeat blood tests were performed and if the white blood cell count remained below 2000, the drug was administered on the same day.

Sodium nucleospermate was administered in a single dose of 75 mg (5 ml of a 1.5% solution) or in a single dose of 150 mg (10 ml of a 1.5% solution) once or over 3-8 days. Before administration, the bottle with the drug was heated to 37 o C, after which the contents of the bottle were administered to the patients subcutaneously for 1 minute.

The effectiveness of the drug was assessed by blood tests (leukocytes) on days 1, 3, 5 and 7, as well as a myelogram on days 6-7 after administration of the drug.

During the study period, patients did not receive additional hemostimulants, vitamins, corticosteroids or blood transfusions.

The research results showed that when using sodium nucleospermate, it was possible to restore the number of peripheral blood leukocytes to 3000 or more in 87% of patients. Recovery of the number of leukocytes was observed on average at 6.3 days. It is characteristic that the increase in the number of leukocytes in the peripheral blood was accompanied by an increase in the content of myelokaryocytes in the bone marrow aspirate by an average of 3.7 times. In all cases, after administration of the drug according to the claimed method, chemotherapy was continued in the planned doses. In all cases, there was no further decrease in the number of leukocytes during chemotherapy.

The effectiveness of using sodium nucleospermate in patients with chronic leukopenia is illustrated in Table. 1.

From the presented table. Table 1 shows that administration of the drug both once and over 3-8 days of mg causes a significant leukostimulating effect in cancer patients.

2. Study of sodium nucleospermate in patients with acute leukopenia.

The study group included patients with “acute” leukopenia who received combination chemotherapy in the inverse mode according to the CAM regimen for small cell lung cancer. Before treatment, patients underwent a complete clinical examination (radiography of the lungs, CT scan of the liver, adrenal glands, brain, skeletal scan, biochemical blood test, myelogram).

Patients with morphologically proven localized SCLC on the first day of treatment received: cyclophosphamide 1.5 g/m2 IV; adriamycin 60 mg/m2 IV; methotrexate 30 mg/m2 i.v.

Starting from the second day of treatment, patients were administered sodium nucleospermate subcutaneously in a single dose of 75 mg (5 ml of a 1.5% solution) or 150 mg (10 ml of a 1.5% solution). Before administration, the bottle with the drug was heated to 37 o C, after which the contents of the bottle were administered to the patients subcutaneously slowly over 1 minute. Administration of the drug was continued for 5 or 10 days.

Blood tests were performed daily from days 2 to 20; A control myelogram was performed later. During the study period, patients did not receive other hemostimulants, vitamins, corticosteroids or blood transfusions.

As a result of the research, the following was shown.

Of the 14 patients who received sodium nucleospermate for 5 or 10 days, the drug was administered in a single dose of 75 mg to 5 patients (12 courses of chemotherapy), and in a single dose of 150 mg to 9 patients (22 courses of therapy). The results are presented in table. 2. As follows from the table, grade 3 leukopenia was detected in 41 (45%) patients, and grade 4 - in 58 (27%) patients. The use of the drug made it possible to carry out chemotherapy without leukopenia or with a slight decrease in the number of leukocytes to grade 1-2 in 20 (36%) patients. A comparison of the effectiveness of sodium nucleospermate depending on the size of a single dose revealed a slight increase in the hemostimulating effect when using a dose of 150 mg (Fig. 1). Profound leukopenia (grade 4) occurred when using a dose of 75 mg in 58% of patients, and when using a dose of 150 mg only in 27% (the differences are not statistically significant).

The recovery time for blood counts in 14 patients with SCLC is presented in Table. 3. In patients who received the drug sodium nucleospermate in a single dose of 75 mg, the average recovery time of leukocytes, calculated from the start of drug administration, ranged from 17.2 days for 1 course to 15 days for 2 and 3 courses. In patients who received a single dose of 150 mg, these indicators were 15.8 - 16.3 - 11.0 days, respectively. The average recovery time for leukocytes, calculated from the end of the course of administration of the drug in the indicated doses, was 7.3 days in the 1st course to 5.8 - 6.0 in the course. The reduction in the recovery time of leukocytes by the 3rd course is apparently associated with the accumulation of the drug or with its cumulative effect on the bone marrow.

Of the 14 patients, grade leukopenia was observed in 12 patients, only 1 had grade 4 leukopenia. The duration of grade 3 leukopenia in patients who received sodium nucleospermate in a single dose of 150 mg for 10 days was reduced from days in the 1st course to days in the 2nd course (Fig. 2). The same indicator, obtained in a group of 19 patients receiving GM-CSF (data from the Chemotherapy Department of the Cancer Research Center, 1993), amounted to days.

In fig. Figure 2 shows the average number of leukocytes and neutrophils in the peripheral blood of patients with SCLC in a semi-logarithmic coordinate system. Curves demonstrating hematopoiesis indices during the use of sodium nucleospermate are shown in comparison with the number of neutrophils calculated for patients who did not receive hemostimulants after similar intensive chemotherapy for SCLC (“placebo”, n-108, Crawford et al., 1991). It can be seen that when using sodium nucleospermate, stimulation of leukocytes occurs due to neutrophils, which is not observed in the “placebo” group. Stimulation is expressed in a decrease in the depth of leuko- and neutropenia by 2 - 2.5 times; absence of grade leukopenia and grade 4 neutropenia; reducing the duration of grade 3 neutropenia from 7 to 5 days.

In table Figure 4 shows a comparative characteristic of hematopoietic restoration in patients with intensive chemotherapy without the use of hemostimulants (placebo) with sodium nucleospermate and with G-CSF. As follows from the data presented, in the “placebo” group, grade 3 neutropenia lasted from 7 to 11 days, while with the use of nucleospermate it was reduced to one day, and with the use of G-CSF to one day. Grade 4 neutropenia in the placebo group lasted for days, with sodium nucleospermate - 1 day, and with G-CSF - 2 days. The maximum neutropenia in the placebo group reached 100 cells, with sodium nucleosperm cells and with G-CSF cells. The period of onset of maximum neutropenia was the same in all comparison groups and was equal to 10 days. The first day of recovery of neutrophils was up to 1000 cells, respectively, and up to 2000 cells, respectively.

When analyzing the effectiveness of sodium nucleospermate in patients after the 1st course of chemotherapy, the following results were noted (Table 5). The number of patients in whom the number of leukocytes reached 3000 cells, and neutrophils 2000 cells per day was 11 people (85%). The number of patients who could undergo the 2nd course of treatment was 8 people (62%).

A study of myelograms in 9 patients showed (Table 6) that the indicators of bone marrow hematopoiesis in all patients before the start of chemotherapy were within normal limits. After chemotherapy against the background of sodium nucleospermate, 6 patients noted a “decrease in myelokaryocytes due to myelocytes and promyelocytes by%, and in three patients a day there was a significant increase in young forms of granulocytopoiesis (promyelocytes and myelocytes) and a corresponding increase in the neutrophil maturation index from 0.8 to 5.7 - 18.0. The relative number of lymphocytes increased by%, while at the same time the number of erythroid germ cells remained unchanged.

It is obvious that the use of sodium nucleospermate in 14 patients with SCLC during intensive chemotherapy made it possible to reduce the depth of leuko- and neutropenia, shorten their duration, conduct chemotherapy without septic complications, and in 63% of patients begin repeated courses of chemotherapy at intervals of days.

Thus, a clinical study of sodium nucleospermate in cancer patients allowed us to draw the following conclusions.

1. Sodium nucleospermate in patients with chronic leukopenia restores the leukocyte composition of peripheral blood (efficacy 87%).

2. In parallel, there is an increase in the number of myelokaryocytes in the bone marrow aspirate (3.7 times).

3. The use of sodium nucleospermate allows not only to restore hematopoiesis, but also to continue chemotherapy as planned.

4. The use of sodium nucleospermate in patients with acute leukopenia during intensive chemotherapy has a hemostimulating effect and helps prevent the development of deep leukopenia and neutropenia and associated septic conditions.

The hemostimulating effect of sodium nucleospermate is associated with stimulation of granulocytopoiesis (promyelocytes and myelocytes), which is manifested in an increase in the neutrophil maturation index by more than 7 times.

An example illustrating the essence of the invention.

Patient Bykov I.A., born in 1939 Outpatient card N 94/5157.

Diagnosis: lymphosarcoma of all groups of peripheral lymph nodes, retroperitoneal lymph nodes of the liver, spleen with leukemia of the type of prolymphocytic leukemia, IV Ast.

Histological conclusion: N 225/94 dated January 13, 1994. Lymphosarcoma from prolymphocyte type cells. 16..03 course of therapy according to the CIPP regimen (leukeran 10 mg per. os, vinblastine 10 mg intravenously on days 1.8, natulan 150 mg per. os days, prednisolone 60 mg/day.

The 2nd course of chemotherapy was not started due to leukopenia 01/IV, 04/IV.

On April 4, 1994, sodium nucleospermate was administered in accordance with the study protocol.

Blood test results: 04/06 platelets, 04/08 platelets.

Thus, the claimed method for correcting the side effects of chemotherapy has the following advantages compared to the known ones.

1. Effectively restores the leukocyte composition of peripheral blood in acute and chronic leukopenia.

2. Stimulates bone marrow hematopoiesis.

3. Allows you to continue adequate chemotherapy as planned.

4. Reduces the risk and frequency of infectious complications.

5. Does not have a negative effect on the body.

All of the above indicates the possibility of widespread use of the claimed method in clinical practice.

Literature 1. Belous A.M. Exogenous nucleic acids and restoration processes.-M.: Medicine, 1974, p..

2. Gershanovich M. L. Complications during chemotherapy and hormonal therapy of malignant tumors. - M.: Medicine 1974, p..

3. Loginov A.S. and others. Reparative effect of nucleic acid preparations in experimental gastric ulcers. Bulletin exp. biol. and med., N 7, 1991.

4. Mashkovsky M.D. Medicines.-M.: Medicine, vol. 2, 1985.

5. Rychnev V.E. Nucleic acids and their therapeutic applications. Medical Affairs, N 8, 1981, p..

6. Slinchak S.M. Oncology. - Kyiv, Vishcha school, 1989, p..

7. Bregni M, S. Siena Breakthrough in cytokine therapy: an overview of GM-CSF. Royal Society of Medicine Services Int.Congress and Symposium Series 1992, N 170, p. 16.

8. P. Gupta et al. Bone Marrow Transplantation, 1992, N 9, p..

9. P. Riikonen, V. Saarinen. Medical and Pediatric Oncology, 1992, N 20, p..

1. A method for correcting depression of bleeding caused by chemoradiotherapy, including the injection of nucleic acid derivatives obtained from the milt of sturgeon fish, characterized in that the drug sodium nucleospermate is used, which is a mixture of sodium salts of polychlorohydrates of derivatives of deoxyribonucleic and ribonucleic acids with the content of nucleic acids in terms of on Na-DNA% with a ratio of nitrogen to phosphorus from 1.3 to 1.8 and 1.8, M.M.000 D, in doses of 0 mg, and before administration the drug is heated, and administration is carried out subcutaneously slowly.

2. The method according to claim 1, characterized in that in case of acute leukopenia, the drug is administered from the second day of using cytostatics according to the CAM regimen throughout the day.

3. The method according to claim 2, characterized in that in case of chronic leukopenia, administration is carried out after a course of chemotherapy once or over the course of days.