Method for treating the cases of ovarian carcinoma relapse

FIELD: medicine.

SUBSTANCE: method involves administering chemotherapy in 1-5 days long courses. The treatment is accompanied with subtotal patient body irradiation with field concentrated in the area from diaphragm vault to feet everyday once a day before every chemotherapy course. Irradiation dose is equal to 0.1 Gy within total dose of 0.8 Gy. The combined treatment is repeated with 2-3 months long pauses to reach remission or total dose of 1 Sv in subtotal patient body irradiation.

EFFECT: enhanced effectiveness of treatment.

 

The invention relates to medicine, more specifically to gynecology, and may find application in the treatment of ovarian cancer.

Taking on the incidence of second place among oncological pathology, ovarian cancer is the leading cause of death. According to foreign authors, every year the world will be diagnosed with ovarian cancer about 166000 women, of whom 101000 die from progression of the tumor process. In Russia from ovarian cancer killed 57% of oncological patients. 70% of newly detected cases is III-IV stage of the disease with a high tendency to recurrence and poor survival rates of patients, despite treatment.

Traditional treatment of primary advanced ovarian cancer consists of cytoreductive surgery and chemotherapy, and conventional treatment of recurrent recognized as chemotherapy. To become involved in ovarian cancer chemotherapeutic agents include alkylating agents, antimetabolites, anthracyclines, inhibitors of topoisomerases, derivatives of platinum and taxanes. Recently, the most widely used in advanced ovarian cancer as second-line chemotherapy have taxanes (paclitaxel, docetaxel, Taxotere) in combination with platinum drugs (cisplatin, carboplatin). Recommended the use of Taxotere at a dose of 75-100 mg/m2in the form of intravenous the infusion in combination with cisplatin at a dose of 75 mg/m 2in one day, what is the course of treatment. The conventional holding 6 courses with an interval of 3 weeks. Frequency objective effect, according to various authors, ranging from 24% to 40% with an average life expectancy of patients from 8 to 10.4 months [Kharitonov T.V., "Modern Oncology", 2002, Vol. 4, No. 3, S.].

In cases of resistance to a number of modern drugs, such as Taxol and cisplatin, the proposed treatment of recurrent ovarian cancer chemotherapy etoposide (Vepesid). If monochemotherapy etoposide is used orally in a single dose of 50 mg/m2within 14 days. Recommended for 6 courses of chemotherapy with etoposide at intervals of 3 to 4 weeks. The frequency of the objective effect of monochemotherapy etoposide ranges from 26% to 34% [Tulandi S.N., "Practical Oncology", 2000, No. 4, p.32-37].

The combination of etoposide with ifosfamide in the treatment of recurrent ovarian cancer, according to Skarios D. et al. (1999), allows to achieve the effect in 26% of cases, with an average life expectancy of patients of 13.7 months.

Closest to the present invention is a method of treatment of relapsed ovarian cancer with the use of combination chemotherapy with etoposide and cisplatin [T. Meyer et al., Annals of Oncology, 2001, Vol.12, 1705-1709] (prototype). In combination with cisplatin etoposide is administered orally at a dose of 50 mg/m21 to 14 and from 29 to 43 days of treatment cycle is, cisplatin - intravenous drip at a dose of 60 mg/m21, 8, 15, 29, 36 and 43 days. Frequency direct effect in the treatment combination of these drugs according to the authors was 44%.

Thus, the frequency of objective clinical effect in this series of works, as with other known methods in the treatment of relapsed ovarian cancer is not large.

The technical result of the present invention is to increase the frequency of objective clinical effect due to the introduction into the treatment scheme Subtotal body irradiation (FREQUENCY), providing a distraction cellular elements of the blood, supporting the proliferation of tumor cells.

This result is achieved by the fact that immediately before each course of chemotherapy is the FREQUENCY of the field from the dome of the diaphragm to stop every day, 1 time a day at a dose of 0.1 Gy to a total dose of 0.8 G and the combined effect is repeated at intervals of 2-3 months to achieve remission or cumulative dose of the FREQUENCY of not more than 1 SV.

Additional implementation of the FREQUENCY in the treatment of patients with ovarian cancer, according to results of our previous studies [Granov A.M., Shutko A.N. Paradoxes of malignant growth and tissue incompatibility, 2002, St. Petersburg, Hippocrates, p.114, 120, 125], provides the appearance of multiple non-lethal radiation damage the cells of normal tissues, requiring reparation proceeding involving lymphocytes. Due to this, in the body there are conditions that require resource redistribution of lymphocytes, performing karpooravalli function, especially in relation to the tumor. Radiation damage of many normal cells distract part of this resource on their own reparation, which reduces the proliferative capacity of malignant tissue. Against this background, the direct effect of a chemotherapeutic agent to cancerous cells would be more efficient.

Based on this newly discovered fact, we held a combined treatment of disseminated ovarian cancer [RF Patent N 2078598, MKI A 61 N 5/10] and, receiving a positive clinical result, I decided to try to apply the tactics of treatment of patients with recurrent disease.

The FREQUENCY in combination with chemotherapy used earlier in the treatment of 37 patients [Yurkova LE, author's abstract on competition of a scientific degree of the doctor of medical Sciences "Systemic radiation therapy in combined treatment of patients with advanced ovarian cancer″, St. Petersburg, 2000, 41]. It SHOULD have been in the form of one course with a single dose of 0.1 Gy and total - 1.0 G, then spent 6 courses of chemotherapy drugs thiotepa and 5-fluorouracil. This resulted in significantly improved directly is installed and the remote results of treatment compared with the control group, which amounted to 127 patients with relapses treated with only chemotherapy courses with thiotepa and 5-fluorouracil. The objective frequency effect increased from 41.7% to 62.2%, three-year survival rate in the group using a FREQUENCY amounted to 16.2%, five-year and 10.8% at zero values of the corresponding values in the control group.

A positive experience with a single FREQUENCY in the treatment of recurrent ovarian cancer was the basis for the study of repeated cycles of the FREQUENCY in the treatment of these patients. We tried to use them in patients with recurrent kidney cancer, located on palliative care. The implementation of these courses proved to be effective in the treatment of the first 3 patients with recurrent, incurable kidney cancer. It made a few (2-4) course, the FREQUENCY with intervals of 2-3 months without any other therapeutic effects. When alone in the form of repeated courses, the FREQUENCY of these patients are living at the time of filing of the application for more than 13 months and continue to be in good condition, while the life expectancy of patients in this category is, according to the statistics, no more than 6-8 months.

These received positive clinical results of the use of repeated courses, the FREQUENCY in the treatment of recurrent kidney cancer has convinced us of the possibility of using not democratic the FREQUENCY in patients with recurrent ovarian cancer. While we spent the cycles of the FREQUENCY of such patients before each course of ongoing chemotherapy.

The use of repeated cycles of the FREQUENCY of prior chemotherapies in the treatment of recurrent ovarian cancer to remission or 1 SV has allowed us to increase the frequency of objective clinical response in these patients until complete clinical remission, which is confirmed by the results of clinical observations. It should be noted that when performing repeated cycles of the FREQUENCY limit total dose of several courses, the FREQUENCY should not exceed 1 SV, due to the requirements of radiation hygiene regulation, which does not allow to call in patients with complications in the form of a symptom-complex of radiation sickness. In this regard, the total dose rate to the FREQUENCY of limited us to 0.8 Gy, and the maximum number of courses the FREQUENCY should not be more than five.

The method consists in the following.

The patient after diagnosis - relapse of ovarian cancer conducted a FREQUENCY range from the dome of the diaphragm to stop with a single dose of 0.1 Gy and a total of 0.8 G. The FREQUENCY of exercise daily for 8 business days and immediately after its completion, conduct a five-day course of chemotherapy drugs etoposide at a dose of 120 mg/m21, 3, 5 days and carboplatin at a dose of 200 mg/m2at 2 and 4 days. This combination of courses the FREQUENCY and Dimiter the FDI is repeated every 2-3 months to achieve remission or a total dose of not more than 1 SV.

The essence of the method is illustrated by the following examples.

Example No. 1. Patient S., 42 years old, was admitted to the Department of surgery gynecology, cnerry 29.04.04 diagnosed with ovarian Cancer III T3cN0M0. Combined treatment with November 2002, the Recurrence of the disease.

From the anamnesis: the Diagnosis of ovarian cancer was installed in October 2002, In Alexander's hospital, St. Petersburg, November 12, 2002, performed the surgery - Hysterectomy with appendages and greater omentum. Histologically (168318-326): "Serous ovarian adenocarcinoma with metastasis to the omentum". With 18.12.02, 28.04.04, the patient received 6 cycles of chemotherapy drugs Taxol on 290 mg, paraplatin on 785 mg In the initial treatment 9.06.2003 was achieved partial remission. In the process of treating a tumor marker CA-125 decreased from 857 u/ml to 110 U/ml Palpable tumor remains in the pelvis decreased from 5×4×1 cm to 3×1,5×1 see

In February 2004, an examination revealed an increase in tumors up to 7×5×2 cm, the appearance of fluid in the pelvic area (according to NMR), the increase of CA-125 to 1379 u/ml, i.e. registered relapse. Regarding relapse 2.03.04 and 1.04.04 received 2 courses of chemotherapy drugs paclitaxel 300 mg, paraplatin 750 mg without effect. Against the backdrop of ongoing chemotherapy continued progression of the disease and, poem the tumor formation in the pelvis, appeared a tumor deep in the cult of the great seal 10×3×2 cm Tumor marker CA-125 has reached 1700 U/ml

When hospitalization 8.05.04 g in cnerry (and/b 1362) for a recurrence of ovarian cancer, it was decided to treat the combination of the FREQUENCY with chemotherapy. The PURITY was performed on 12.05.04 26.05.04, gamma-therapy apparatus ROCUS-M two anterior-posterior fields from the dome of the diaphragm to stop when RIP 170 cm in mobile mode with sector rotation 346°-60° and the speed of rotation 0.77 deg/sec. Irradiation was performed daily at a dose of 0.1 Gy to a total dose of 0.8 G. After the FREQUENCY with 31.05.04 on 4.06.04, a course of hemoterapia drugs etoposide and carboplatin. Etoposide was administered intravenously 200 mg in 1, 3, 5 days of the course. Carboplatin 310 mg in 2 and 4 days. As a result of the treatment decreased the tumor size nodes in the pelvis with 7×5×2 cm to 4×3×1.5 cm and in the cult of the greater omentum with 10×3×2 cm to HH see Tumor marker decreased to 598 U/ml

Re-hospitalization in cnerry 2.07.04, (b 2148). Given in the month of may a positive trend, it was decided to repeat the combination of the FREQUENCY and chemotherapy. With 5.07.04 on 14.07.04, conducted a FREQUENCY in the same modes, and with 15.07.04 on 19.07.04, - chemotherapy drugs etoposide in a total dose of 600 mg and carboplatin at a dose of 520 mg of the Effect of the treatment estimates is n when the next arrives. Gynecological examination showed reduction of tumor in the pelvis with 6×4×2 cm to 3×3×1.5 cm Tumor deep in the cult of the greater omentum is not detected by palpation. CA-125 dropped to 294 U/ml

Re-admission to cnerry 8.09.04, (b 2288). For the third time made the combination of the FREQUENCY and chemotherapy. The FREQUENCY carried out by the method described above with 23.09.04 on 4.10.04, Chemotherapy drugs etoposide (550 mg) and carboplatin (530 mg) was implemented with 11.10.04 on 15.10.04, as a result of the treatment of CA-125 decreased to 227 U/ml When gynecological survey found only tumor site in the pelvis 3×3×1.5 cm

When entering cnerry 27.12.04, (and a/b No. 3761) for the fourth time spent combined treatment. The PURITY was carried out with 27.12.04, 15.01.05, in a total dose of 0.8 G, chemotherapy with etoposide (600 mg) and carboplatinum (600 mg) - 17.01.05 on 21.01.05, CA-125 dropped to 204 U/ml

Thus, the patient after two courses of combination of the FREQUENCY and chemotherapy (8.09.04,) was awarded partial remission that lasts more than 6 months with further improvement. Treatment the patient continues.

To compare patient F. (and a/b No. 1635), with a similar stage ovarian cancer (III T3cN0M0) and similar to the primary treatment in cnerry (surgery and 6 cycles of chemotherapy with Taxol and paraplatin), recurrence of disease is in the pelvis (tumor node 6× 4×2 cm) in the beginning of 2004 was held chemotherapy drugs etoposide in a total dose of 700 mg and carboplatin at a dose of 600 mg Effects were noted. Gynecological examination in the month identified further growth of the tumor in the pelvis, the appearance of ascites and metastases in the thickness of the anterior abdominal wall. CA-125 increased from 5196 u/ml to 28 530 U/ml Observed in the generalization of the tumor process and after 7 months - the death of the patient.

Example No. 2. Patient C., 41, was admitted to the Department of surgery gynecology, cnerry 4.10.04 diagnosed with ovarian Cancer IV T3cN1M1. Combined treatment with February 2003, the Recurrence of the disease.

From the anamnesis: the Diagnosis of ovarian cancer was installed in January 2003 In cnerry February 6, 2003, the operation - Supracervical amputation of the uterus with appendages and greater omentum. Histologically (171045-052): "Serous cystadenocarcinoma with ovarian metastases in the omentum". With 7.03.03, 25.08.03, the patient received 6 cycles of chemotherapy drugs Taxol (260 mg, paraplatin on 783 mg In the initial treatment 17.07.2003 was achieved complete clinical remission. In the process of treating a tumor marker CA-125 decreased from 797 u/ml to 14 U/ml Palpable tumor remains in the pelvis and abdomen, ascites, hydrothorax completely disappeared.

Planned hospitalization in cnerry 4.10.04, (b 1362). When about is ladouanie in the pelvis revealed a tumor site, size HH cm, a small amount of fluid and metastatic lesion of the pelvic lymph nodes on the left (according to NMR). CA-125 increased from 14 u/ml to 54 u/ml, i.e. registered relapse. A decision was made regarding relapse to perform a combination treatment, including the FREQUENCY and chemotherapy. The FREQUENCY conducted 31.10 on 20.10.04, gamma-therapy apparatus ROCUS-M two anterior-posterior fields from the dome of the diaphragm to stop when RIP 170 cm in mobile mode with sector rotation 346°-60° and a rotation speed of 0.8 deg/sec. Radiation, as in the first case, performed daily at a dose of 0.1 Gy to a total dose of 0.8 G. After the FREQUENCY with 25.10.04 on 29.10.04, a course of hemoterapia drugs etoposide (600 mg) and carboplatin (500 mg). As a result of treatment the tumor site in the pelvis decreased from 6×5×4 cm to 5×to 3.5×2.8 cm, disappeared ascites, tumor marker decreased from 54 to 35.6 U/ml

Re-hospitalization in cnerry 22.12.04, (b 3767). Given the previously positive trend, it was decided to repeat the combination of the FREQUENCY and chemotherapy. With 27.12.04 on 15.01.05, conducted a FREQUENCY in the same modes, and with 17.01.05 on 21.01.05, - chemotherapy drugs etoposide in a total dose of 600 mg and carboplatin at a dose of 500 mg. Effect of the treatment evaluated in outpatient examination in March 2005, During gynecological examination, 15.0305 the observed disappearance of the tumor in the pelvis. CA-125 from 10.03.05, - 17 u/ml, i.e. within the normal range. The patient achieved complete clinical remission in the two repeated courses the FREQUENCY and chemotherapy.

To compare patient With. (and a/b No. 3730)treated similar to the primary treatment in cnerry (surgery and 6 cycles of chemotherapy with Taxol and carboplatinum) about ovarian Cancer IV 3N0M1, Lucena us in connection with recurrence in the pelvis (tumor site 8×6×4 cm) two courses of chemotherapy drugs etoposide with directional dose of 550 mg and carboplatin at a dose of 500 mg. of the Effect of the treatment were noted. Tumor process progressed. When viewed through the month discovered that the entire pelvis with access to the abdomen to the navel made no move tumor conglomerate. In the field stump greater omentum is also defined tumor performing upper abdomen. CA-125 increased from 466 to 1642 E/ml of the patient's Condition is recognized as incurable, is only symptomatic treatment.

Currently, the proposed method of treatment used in the treatment of 6 patients with recurrent ovarian cancer. One patient received 4 cycles of combination of the FREQUENCY with chemotherapy with etoposide and carboplatin, one is 3, three patients 2 and one currently received 1 cycle with distinct positive dynamics. In 5 of 6 Strait is Chennai patients had a positive effect in the form of complete remission (2 observations), partial remission (2 observations), stabilization of the tumor process (1 observation). Not marked clinical effect in 1 patient.

Earlier we Lucena group of 3 similar patients with recurrent ovarian cancer only repeated courses of chemotherapy (2-3) drugs of etoposide and carboplatin without the use of a FREQUENCY. The effect of stabilization was noted only in one. In the other two cases, despite treatment, continued progression of the disease.

Thus, the proposed method of treatment has allowed to achieve immediate effect in 83.3% of cases compared with the frequency of clinical effect in traditional chemotherapy, is 33.3%.

The proposed method of treatment in comparison with the known and the prototype has the following advantages:

1. allows you to significantly increase the frequency of the objective effect (26-44% to 83%) due to the introduction into the treatment scheme the FREQUENCY.

2. easily tolerated by patients, and in the presence of General symptoms (rise in body temperature, anorexia) due to intoxication on the background of the progression of the tumor process after the first session it SHOULD normalize the condition of patients and improves appetite.

The proposed method of treatment developed in the Department of surgery gynecology, cnerry together with the laboratory of "Increasing efficiency of radiation therapy" cnrri and Rachel clinically tested with a positive result. Currently in the Department of surgery lab cnerry treated this way 6 patients with recurrent ovarian cancer with the achievement of the objective frequency effect to 83,3%.

The method of treatment of relapsed ovarian cancer through chemotherapy courses for 1-5 days, characterized in that immediately before each course of chemotherapy perform Subtotal-body irradiation the patient (FREQUENCY) field from the dome of the diaphragm to stop daily 1 time per day in a dose of 0.1 Gy to a total dose of 0.8 G and the combined effect is repeated at intervals of 2-3 months. to achieve remission or cumulative dose of the FREQUENCY of not more than 1 SV.



 

Same patents:

FIELD: medicine.

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1 tbl

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4 cl, 4 dwg, 6 tbl

FIELD: medicine.

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1 dwg

FIELD: medicine, pediatrics, hematology.

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4 cl, 5 ex

FIELD: medicine, oncology.

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3 ex

FIELD: oncology.

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2 ex

FIELD: medicine.

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1 cl, 1 dwg, 1 ex

FIELD: medicine, oncology.

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1 ex

FIELD: medicine, oncology.

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1 ex

FIELD: medicine.

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22 cl, 8 dwg

FIELD: medicine.

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EFFECT: higher efficiency of radiation therapy.

2 ex

FIELD: medical engineering.

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3 cl, 3 dwg

FIELD: medicine.

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EFFECT: higher efficiency of therapy.

1 ex

FIELD: experimental medicine, oncology, biology.

SUBSTANCE: invention relates to a method for inhibition of tumor growth using radiation therapy as ionizing radiation with additional administration of mixture of octa-4,5-carboxyphthalocyanine sodium cobalt salt or oxocobalamine with sodium ascorbate in the ratio = (1:10)-(1:30). Method of combined using irradiation and indicated mixture of substances provides enhancing the effectiveness of anti-tumor treatment resulting to 70-100% recovery of experimental animals and reducing radiation loading and toxicity.

EFFECT: improved method for inhibition.

2 tbl, 3 dwg, 3 ex

FIELD: medicine, oncology.

SUBSTANCE: the method deals with applying chemopreparations incubated with autolymph and radiation therapy. Lymph taken out of patient's thoracic duct should be centrifuged for 30 min at 2200 rot./min, lymphatic plasma should be taken and frozen at -40 C, lymphatic formic elements should be incubated in a thermostat at 37 C for 1 h together with chemopreparations by a certain scheme to be reinfused for a patient intravenously by drops according to the given scheme. Then, 2 wk later, one should perform therapy with a split course of distance gammatherapy at single focal dosage (SFD) of 4 Gy. At the first stage one should apply per 2 Gy twice daily at 4-5-h-long interval 5 times weekly, at achieving focal dosage of 28 Gy it is necessary to have a week-long interval. Then radiation therapy should be continued but SFD of 4 Gy should be applied at once. One should fulfill 3 fractions of irradiation per a week, there are 6 fractions during the second stage, totally. Total focal dosage (TFD) per the whole course of irradiation corresponds to 52 Gy. About 4 wk after radiation therapy one should defrost lymphatic plasma to incubate it with the same chemopreparations in a thermostat at 37 C for 1 h to be then reinfused for a patient intravenously by drops. The method enables to decrease tumor volume and tumor process metastasing without any operative interference.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: medicine, oncology.

SUBSTANCE: before irradiation it is necessary to cool the tumor to achieve the temperature of freezing at clinically detectable border between the tumor and healthy tissue to perform irradiation directly after natural tissue defrosting with a single focal dosage (SFD) being 2-2.5 Gy daily for 5 d a week at 2-d-long interval to achieve total focal dosage (TFD) of 60-65 Gy. Moreover, the area of healthy tissue should be protected with a shielding applicator - a lead plate - during irradiation. The present innovation enables to maximally keep anatomical relief and function of local tissues.

EFFECT: higher efficiency of therapy.

1 cl, 4 ex

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