RU2257233C2 - Method for treating inoperable pulmonary cancer - Google Patents

Abstract

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.

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Description

The invention relates to medicine, namely to oncology, and can be used for the treatment of patients with lung cancer, which is contraindicated in surgical treatment.

A known method of treating lung cancer ("Antitumor chemotherapy" under the editorship of NN Perevodchikova, M., "Medicine", 1986, p. 45-47) by intravenous administration of various combinations of chemotherapeutic agents. For inoperable tumors, an intravenous chemotherapy regimen is used: cyclophosphamide - 500 mg / m ² , adriamycin - 60 mg / m ² , vincristine - 1.4 mg / m ² with repeated administration of a course dose of drugs after 4 weeks.

However, the effectiveness of using this and similar schemes for locally advanced inoperable lung cancer does not exceed 25-30% according to the authors, and, as a rule, it is not possible to achieve complete regression at all. Remission in this case lasts an average of 4-6 months.

There is a method of treating inoperable lung cancer by modifying radiation therapy with a gas mixture (Ovchinnikov V.A., Burmistrova G.V. Hypoxiradiotherapy of lung cancer in a dynamic multifraction dose: immediate results. Mat I congress of oncologists of the CIS countries. Part II. Moscow. 3- December 6, 1996). Patients with inoperable squamous cell lung cancer were treated under conditions of inhalation of a gas hypoxic mixture containing 10% oxygen and 90% nitrogen during a radiation treatment session: 0.1 Gy - a break of 3 minutes, 1.9 Gy, the next session after 6 hours, 0 , 1 Gy, after a break of 3 minutes - 1.9 Gy. The daily dose was 4 Gy, 20 Gy per week. The total focal dose at stage 1 28 Gy. At the second stage, respectively - 0.1 Gp - a break of 3 minutes - 0.9 Gy, the next session after 6 hours, 0.1 Gy - a break of 3 minutes - 0.9 Gy. Daily dose of 2 Gy, per week - 10 Gy. The total dose in stage 2 is 30 Gy. The interval between the two stages ranged from 21 to 40 days (an average of 26 days).

However, after this method of treatment, 33% of patients completed the treatment without effect, and among the total number of patients, radiation reactions were observed in 21% of patients in the form of threshold erythema and dry radiodermatitis, radiation esophagitis was in 12%. General radiation reactions: nausea, general weakness, loss of appetite occurred in 29% of patients.

The aim of the present invention is to improve the results of conservative treatment of patients with inoperable lung cancer.

The goal was achieved in that patients with lung cancer began treatment with drainage of the thoracic duct, collecting lymph and dividing it into fractions. Then the patients were injected with chemotherapy pre-incubated with lymph suspension, lymph plasma was frozen and stored. After 5 injections of chemotherapy on lymph suspension, radiation treatment was performed to the patients two weeks later. 6 weeks after radiation therapy, chemotherapy was carried out with incubated lymph thawed plasma, with 3-5 such injections.

The invention is new because it is not known from the level of medicine in the field of oncology in the treatment of inoperable lung cancer with chemotherapeutic agents in combination with radiation therapy. The novelty of the invention lies in the fact that in the treatment of lung cancer, chemotherapeutic agents are administered on the patient’s autolymph shaped elements, radiation treatment is performed, and then chemotherapy is performed on the thawed plasma of the patient’s lymph. The invention has an inventive step, since it is not known to an oncologist in this field and does not explicitly follow from the level of clinical oncology.

There are no indications of a similar method for improving the immediate results of treating inoperable lung cancer in accessible sources of information from Russia, the CIS countries and abroad.

The invention is industrially applicable, as it can be repeatedly reproduced and applied in healthcare, in medical institutions of a specialized profile.

The method is as follows.

With a cancer patient, the thoracic duct is easily drained, lymph is collected, centrifuged for 30 minutes at 2200 rpm. Then the lymph plasma is frozen at a temperature of -40 ° C, followed by storage at -18 ° C. Lymph suspension is incubated with cytostatics: cisplatin - 150 mg, doxorubicin - 50 mg, cyclophosphamide - 1000 mg in a thermostat for 1 hour, at a temperature of 37 ° C, and then administered to the patient intravenously.

Before the introduction of cisplatin rehydration is carried out in a standard volume. In total, 5 similar courses of fractional autolymphochemotherapy are carried out, administering chemotherapy drugs after their incubation with lymph suspension, and freezing the lymph plasma. 2 weeks after the last administration of chemotherapy on lymph suspension, patients undergo radiation therapy. After 4 weeks after radiation treatment, repeated chemotherapy courses are carried out. To do this, lymph plasma is thawed stepwise in portions, chemotherapeutic agents: cisplatin - 150 mg, doxorubicin - 50 mg, cyclophosphamide - 1000 mg, incubated with thawed plasma of lymph in a thermostat for 1 hour at a temperature of 37 ° C, and then administered to the patient intravenously, dropwise.

For evidence, we provide an extract from case histories confirming the clinical effect of treatment by the proposed method.

Extract from the medical history N 17856 \ n, an example.

Patient M, born in 1930, was admitted to the thoracic department of the RNII on 12.19.2001 with complaints of frequent unproductive cough, shortness of breath during physical exertion, weakness, hemoptysis, pain in the left side of the chest, subfebrile temperature, hoarseness.

As a result of a clinical and radiological examination, the diagnosis was made: central cancer of the upper lobe of the left lung (T2N2M0).

From the anamnesis of the disease it was found that the first signs of malaise appeared 3 months ago, when for the first time the patient noted weakness, dry cough, subfebrile temperature, then chest pains appeared. At the end of November 2001, he went to the doctor in the district clinic due to hoarseness, was examined, a tumor was found in the left lung. The patient was consulted by the district oncologist and sent to the RNII.

An X-ray examination revealed a tumor of the upper lobe of the left lung up to 4 cm in diameter, with metastases to the lymph nodes of the root and mediastinum. Cytological verification of the tumor (squamous cell carcinoma) was obtained by fibrobronchoscopy with biopsy. Given the degree of spread of the process, low FVD, the patient's condition was considered inoperable. ALCHT was recommended.

12.24.01 the patient underwent surgery for drainage of the thoracic lymphatic duct. Then the patient underwent a course of ALXT according to the following procedure:

- lymph was taken in a standard container with the preservative Glucocon 500 \ 300 glucicir in the amount of 500 ml, with a diet prescribed for the patient, during the collection of lymph, including the exclusion of foods with a relatively high fat content, heavy drinking;

- centrifugation of lymph for the purpose of separation on the apparatus "PC-600". Mode: 2200 rpm, 30 min, at a temperature of 36 ° C.

- the lymphoplasm obtained as a result of separation was subjected to freezing at a temperature of -40 ° C with subsequent storage at 18 ° C;

- Lymph suspension was incubated with cytostatics in a thermostat for 1 hour, at a temperature of 37 ° C, and then was administered to the patient in a drip.

The treatment was carried out according to the CAP scheme. Before the introduction of cisplatin in all cases, rehydration was carried out in a standard volume. In total, over 5 injections over 20 days from 12.25.01 with an interval of 3 days, the patient was administered 300 mg of cisplatin, 3000 mg of cyclophosphamide, 150 mg of doxorubicin. A single dose for cisplatin was 150 mg, doxorubicin - 50 mg, cyclophosphamide - 1000 mg.

In the process of ALCH, the patient noted gastro-intestinal disorders. After the third administration of chemotherapy, the patient significantly decreased cough, normalized body temperature, and after chemotherapy, pain in the chest and hoarseness disappeared. On control radiographs 14 days after the end of ALXT, the tumor is reduced by one third of the original size. However, the location and spread of the tumor process did not allow the patient to undergo radical surgery and radiation therapy was proposed.

From January 28, 2002, the patient was given a split DHT course on the ROKUS-M apparatus. A single focal dose (ROD) was 4 Gy. At the first stage of the split course, ROD was delivered to the irradiation zone at 2 Gy 2 times a day with an interval of 4-5 hours 5 times a week. Upon reaching a focal dose of 28 Gy, a 2-week break was taken. After the break, radiation therapy was resumed under the same technical conditions, but ROD 4 Gy was administered simultaneously. 3 irradiation fractions were performed per week. A total of 6 fractions were carried out in the second stage. The total focal dose (SOD) for the entire split irradiation rate was 52 Gy, which corresponds to 62.5 Gy of classical fractionation.

After 1 month after the end of radiation treatment, from 15.04.02 the patient was given an adjuvant XT course on preserved autolymphoplasm according to the following procedure:

- after thawing, the lymphoplasm was incubated with a cytostatic in the thermostat for 1 hour at a temperature of 37 ° C, followed by the introduction of a drip into the patient.

In total, over 4 injections over 16 days with an interval of 3 days, the patient received 200 mg of cisplatin, 2000 mg of cyclophosphamide, 100 mg of doxorubicin. During treatment, the patient noted nausea, leukopenia of the II degree.

The patient lives for 1 year without signs of progression of the process and distant metastasis.

The technical and economic effect of the use of the "Method for the treatment of inoperable lung cancer" is that the immediate results of treatment and the quality of life of patients are improved; pathological side effects of antitumor therapy are reduced.

Claims (1)

A method of treating inoperable lung cancer, including the introduction of chemotherapy drugs incubated with autolymph, and radiation therapy, characterized in that the patient’s lymph taken from the thoracic duct is centrifuged at 2200 rpm for 30 minutes, lymph plasma is collected and frozen at -40 ° C, shaped elements the lymphs are incubated in an incubator at 37 ° C for 1 h with the chemotherapeutic drugs used in the CAP scheme and the patient is re-infused intravenously according to this scheme; after 2 weeks, radiation treatment is carried out - with a split course of remote gamma-therapy with a single focal dose of 4 Gy, at the first stage of the split-off course, 2 Gy are delivered to the irradiation zone 2 times a day with an interval of 4-5 hours 5 times a week, upon reaching the focal dose 28 Gy make a 2-week break, after the break, radiation therapy is resumed, but a single focal dose of 4 Gy is administered simultaneously, 3 fractions of radiation are performed per week, 6 fractions are performed at the second stage, the total focal dose for the entire split radiation course is 52 G ; 4 weeks after radiation treatment, lymph plasma is thawed, incubated with the same chemotherapeutic agents in an thermostat at 37 ° C for 1 h, and the patient is re-infused intravenously.