Treatment for ovarian cancer is complex: surgical, chemotherapeutic, radiation and hormonal.
Treatment for malignant ovarian tumors should always begin with surgery (with the technical feasibility of the operation, i.e., with sufficient mobility of the tumor conglomerates). If this is not possible, treatment begins with chemotherapy, and the operation is performed later, when the tumor decreases and becomes more mobile, and the general condition of the patient improves. The operation of choice for technical accessibility (I-III stage) is supravaginal amputation or extirpation of the uterus with appendages, removal of the greater omentum, as well as the maximum removal of metastatic cancer nodes. With the widespread process, the main task is to remove the tumor masses as much as possible, provided that the latter are removed easily, without injury, so as not to lead to a quick generalization of the process. With advanced ovarian cancer in some patients, surgery may be limited to removing only a large omentum infiltrated by the tumor, which helps to slow the accumulation of ascitic fluid.
If a relapse is suspected, relaparotomy is necessary.
In the complex treatment of various stages of ovarian cancer, drugs from the group of alkylating compounds, ethyleneimine derivatives – etymidine, benzotef, thiophosphamide (thioTEF), as well as cyclophosphamide (endoxan) are used. Crucial in inhibiting tumor growth is the inhibitory effect of ethyleneimine derivatives on nucleic acid metabolism and glycolytic processes.
Indications for use of drugs: stage I-II ovarian cancer after radical surgery to prevent the development of metastases and relapses; stage III ovarian cancer after non-radical removal of the tumor in order to achieve the reverse development of the remaining tumor elements scattered throughout the peritoneum of metastases, as well as the prevention of ascites; stage IV ovarian cancer with contamination of the abdominal organs (cancerous peritonitis, ascites and metastases in other organs).
Contraindications to the use of chemotherapy: terminal stages of the disease, general serious condition, cachexia; low levels of white blood cells (below 3000 in 1 mm3), platelets (below 150,000 in 1 mm2) and hemoglobin (below 40%); severe concomitant diseases (active tuberculosis, glomerulonephritis, severe circulatory failure, parenchymal hepatitis).
Chemotherapy is carried out in courses. The number of courses is determined by the condition of the patients and the effect of treatment.
In the first year, the highest concentration of the drug in the body should be created. After 6 weeks, repeat the course to consolidate the primary effect. Subsequent courses are held in 3-4-6 months.
Routes of administration: intravenous, intraarterial, intramuscular, into the pleural and abdominal cavities and directly into the tumor. The main route of administration is intravenous. Drugs are administered every other day or two days in a row with a one-day break, depending on their tolerance. A single dose of etymidine is 6 – 9 – 12 mg, benzotef – 24 – 48 mg, thiophosphamide – 10-20 mg, cyclophosphamide 200-400 mg, phenamet 0.5-1.5 g orally, imidafen 60 mg orally after meals daily.
The drug is injected into the abdominal cavity through a drainage (polyethylene or rubber) tube, which is inserted during stomach cutting, or through a trocar after removal of ascitic fluid. In the abdominal cavity, drugs are administered daily or every other day for 12-16 days, in the pleural cavity – 2-4 days after removal of the fluid. The drug is injected into the cavity in a double dose.
Intratumoral administration of drugs is carried out through the posterior vaginal fornix. One or two doses of the drug are administered. Administration is repeated after 2-4 days (4-6 administrations in total). Recently, intralymphatic administration of chemotherapy drugs has been used (A.I. Milyanovsky). The most effective regional introduction of chemotherapy (perfusion in the artery, the nourishing organ). Currently, the administration of shock doses (ten or more) of cytostatic drugs into the lymphatic duct (lymphatic infusion) and intraarterial (arterioinfusion) is used.
It is recommended to combine the route of administration:
intravenous and intracavitary; intravenous and intratumoral; intravenous and intralymphatic. According to domestic and foreign authors, during the treatment process, the drug should be changed, i.e., separate courses should be carried out with various drugs in order to prevent the resistance of cells to this chemotherapy drug. The introduction of two or three drugs at the same time (polychemotherapy) is much more effective if they are low-toxic (chemotherapy and antiblastic antibiotics, benzotef and cyclophosphamide). Each of these drugs acts on different metabolic links, which provides a higher cytotoxic effect. The course dose of etymidine is 120-180 mg, benzotef – 500-600 mg, thiophosphamide -250-400 mg, cyclophosphamide up to 12 g, phenamet 20-40 g, imidafen – 17 g. A strict individual dosage of drugs is required depending on the effectiveness and effect on hematopoietic system. Chemotherapy should be carried out under the strict control of blood and urine. The choice of a chemotherapeutic drug for a second course of chemotherapy or for a relapse of the disease is carried out taking into account all the details of previously conducted chemotherapy. It should be borne in mind that the effectiveness of thioTEFa with repeated administration is reduced and its appointment more than two times or, as an exception, three times to the same patient is not desirable. Cyclophosphamide may be equally effective with repeated use, and the duration of remissions may increase. For the treatment of patients with relapses, other drugs can also be used (sarcolysin, chlorambucil, tramimon, phenamet, imidafen, lofenal, etc.), as well as their combinations. Intolerance to one or another drug (usually cyclophosphamide) is rare and manifests itself after its first administration by nausea, vomiting, pain in the hypogastric region, sharp weakness, fever, lowering blood pressure. In such cases, the administration of this drug must be discontinued and symptomatic therapy (cardiac drugs), antibiotics, antipyretics, diet, etc.), as well as vitamins (thiamine, pyridoxine, ascorbic acid, cyanocobalamin), diprozinfen or chlorpromazine. The most common complications of chemotherapy are bone marrow depression in the form of leukopenia and thrombocytopenia, as well as anemia. Previous radiation therapy or chemotherapy causes an increased sensitivity of the hematopoietic organs to chemotherapeutic drugs. The fight against leuko- and thrombocytopenia is carried out by the timely appointment of hemostatic stimulants (leucogen, pentoxyl, tezan, sodium nucleinate, serotonin and ACS) by systemic transfusions of canned blood (100 ml 1-2 times a week), leukocyte and platelet suspension (50 ml 1 time per 5-7 days 4-6 times for the entire treatment period). With severe leukopenia, preference should be given to freshly citrated blood, which is the best stimulator of hematopoiesis. In similar cases, severe and persistent leuko- and thrombocytopenia have to resort to an autogenous or heterogeneous bone marrow transplant. Irrational intensive chemotherapy, not controlled by indicators of the state of peripheral blood and bone marrow, can cause irreversible aplasia of the bone marrow and lead to the death of the patient. With a decrease in the number of leukocytes to 3000 in 1 m3 and platelets to 150 000, the administration of chemotherapy should be temporarily stopped. The use of cyclophosphamide is possible allopecia. Hair growth, as a rule, is restored in 2-2.5 months after the termination of chemotherapy. The rarer complications of cyclophosphamide treatment include cystitis, sometimes hemorrhagic in nature. According to I. D. Nechaeva, the average life expectancy of patients who underwent chemotherapy after radical surgery was 1.9 times higher than the life expectancy of patients who underwent external radiation after radical surgery. Therefore, after radical surgery , chemotherapy is most appropriate. Chemotherapy after non-radical operations and in inoperable patients helps to prolong their life. The survival rate of such patients is 10 times greater compared with patients who did not receive chemotherapy after surgery. In some cases, with a far advanced tumor process, when it is impossible to perform any rational surgical intervention, chemotherapy is prescribed as an independent treatment method. In the absence of a clinical effect, it is more advisable to refuse to continue chemotherapy. In patients who underwent chemotherapy after the initial successful treatment, a later relapse of the disease is noted. I. D. Nechaeva (1973) recommends the following regimen for conducting preventive chemotherapy courses: the first – 2 months after the end of the initial treatment; the second – 4 months after the first preventive course; the third – after 6 months. Thus, preventive chemotherapy continues for three years after the end of the initial treatment. If relapse occurs during this period, a second course of treatment should be started.