RU2461375C1 - Method of combination treatment of patients with locally advanced stomach cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology, and concerns a method of combination treatment of locally advanced stomach cancer. The method involves two courses of systemic polychemotherapy (PCT) followed by a radical surgery. The pre-operative PCT follows the scheme FOLFOX 6: oxaliplatin - 85 mg/m² 2-hour intravenous infusion in the 1st day; leucovorin - 200 mg/m² 2-hour intravenous infusion in the 1st and 2nd days; 5-fluorouracil - 400 mg/m² intravenous bolus administration in the 1 st day then 5-fluorouracil - 2.4-3.0 g/m² 46-hour intravenous infusion; the course is repeated in 2-3 weeks.

EFFECT: invention provides improved remote results of the combined treatment of locally advanced stomach cancer ensured by reduced number of complications, as well as prevention of progression of tumour process and remote metastases.

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Description

The invention relates to medicine, in particular to oncology, and relates to methods for the combined treatment of locally advanced gastric cancer.

A known method for the combined treatment of locally advanced cancer of the stomach, including radical surgery in combination with intraoperative radiation therapy (IOLT). Intraoperative irradiation, as a component of combined treatment, undoubtedly increases the effectiveness of treatment, since the focal dose is administered directly on the bed of the removed tumor of the regional metastasis zone, which, according to published data, improves the long-term results of treatment of patients. However, this method of combined treatment does not prevent the progression of the tumor process due to the development of distant metastases [1, 2].

Closest to the proposed is a method of combined treatment of locally advanced cancer of the stomach, including surgical treatment and drip of 5-fluorouracil into the portal vein. The day before surgery, the thoracic lymphatic duct is drained in the neck, then the portal vein is catheterized before surgery and perioperative chemotherapy with 5-fluorouracil at a dose of 800-1000 mg is started. The disadvantage of this method is the need for drainage of the thoracic lymphatic duct and portal vein, which can lead to an increase in the number of postoperative complications. [3].

A new technical task is to reduce complications, improve the long-term results of the combined treatment of patients with locally advanced gastric cancer, prevent the progression of the tumor process and distant metastasis.

To solve the problem in a method of combined treatment of patients with locally advanced gastric cancer, including chemotherapy followed by radical surgery, patients undergo two courses of systemic chemotherapy (PCT) before surgery according to the following FOLFOX 6 scheme: Oxaliplatin - 85 mg / m ² 2- hourly intravenous infusion on the 1st day, Leucovorin - 200 mg / m ² 2-hour intravenous infusion on the 1st, 2nd day, 5-Fluorouracil - 400 mg / m ² intravenously jet on the 1st day, then 5 -fluorouracil - 2.4-3.0 g / m ² 46-hour intravenous infusion, repeat This course is carried out after 2-3 weeks.

The method is as follows: the patient in the preoperative period at the first stage is given two courses of PCT according to the FOLFOX 6 scheme: Oxaliplatin - 85 mg / m ² 2-hour iv infusion on the 1st day, Calcium folinate (Leucovorin) - 200 mg / m ² 2-hour iv infusion on the 1st, 2nd day, 5-Fluorouracil - 400 mg / m ² iv in a stream on the 1st day, then 5-fluorouracil - 2.4-3.0 g / m ² 46-hour iv infusion. A break between courses is 2-3 weeks. Then, an effect is evaluated 3 weeks after completion of the second course with subsequent radical surgery (gastrectomy, subtotal distal gastric resection with lymph node dissection D2).

In the case of achieving stabilization of the process after two courses of PCT according to the described scheme, further tactics consisted in performing a radical operation.

In the case of the progression of the process that is detected during the follow-up examination after the first course of PCT, a radical operation is performed after the end of the first course of chemotherapy.

The rationale for the method

The proposed treatment regimen allows to reduce the extent of tumor infiltration in the organ and thereby reduce the volume of tissue removed; and also reduce the biological activity of tumor cells, which prevents the dissemination of the tumor during surgery, the progression of the tumor process in the form of distant metastases. Most chemotherapy regimens are highly toxic and can adversely affect the course of the perioperative period. A number of drugs, such as eloxatin, irinotecan, capecitabine, which have moderate and well-controlled toxicity, have been shown to be active in the treatment of metastatic gastric cancer [3], which allows them to be included in the combined treatment regimen for locally advanced gastric cancer.

The proposed combination of doses and the administration of cytostatics are based on experimental and clinical studies.

Oxaliplatin (eloxatin) is an antitumor drug derived from platinum, in the molecular structure of which the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane. Biotransformed aqueous derivatives of oxaliplatin, interacting with DNA by the formation of inter- and intra-traction bridges, inhibit DNA synthesis, this is due to the cytotoxicity of the drug and the antitumor effect.

5-Fluorouracil is an antitumor drug from the group of antimetabolites. It inhibits the process of cell division by blocking DNA synthesis (due to inhibition of the activity of the enzyme thymidylate synthetase) and the formation of structurally imperfect RNA (due to the introduction of fluorouracil into its structure). Indications for use: esophageal cancer, gastric cancer, pancreatic cancer, colon cancer, liver cancer, breast cancer, ovarian cancer, uterine cancer.

Leucovorin - folinic acid, which is a reduced form of folic acid, is easily converted into other reduced derivatives of folic acid (dihydro- and then tetrahydrofolic), which are necessary for the synthesis of thymine and purines, and therefore DNA, RNA and proteins. Helps to fill up the deficiency in the body of folic acid. It has a hematopoietic effect, stimulates the growth of rapidly renewing tissues (including the gastrointestinal mucosa). Being an antidote to folic acid antagonists, it prevents damage to bone marrow cells, ensures the safety of hematopoiesis and allows the use of cytostatics, including and 5-fluorouracil in high doses necessary for chemotherapy of tumors.

It is also important that the profile of non-hematological toxicity of drugs, including neurotoxicity, does not match. The suggested doses of drugs are most effective for this combination of drugs. A break between chemotherapy courses and before surgery for a period of 2 weeks, respectively, is necessary to completely stop the occurring adverse reactions from the hematopoietic system, urinary system. The use of two courses of chemotherapy allows us to evaluate the effectiveness of this combination of drugs in each case and, based on an assessment of the objective effect of the two courses of chemotherapy, determine the further treatment tactics.

Examples of the method:

Example 1

The history of the disease №09423. Patient P., 67 years old, has been in the department since 05/05/10. on 06/23/10 with a diagnosis of gastric cancer, subtotal lesion, stage III. Histology No. 6711 - 17/10 of 04/06/10: low-grade adenocarcinoma.

When computed tomographic examination (before the start of chemotherapy courses), the tumor subtotally affects the stomach, there is an uneven thickening of the walls, starting from v / 3 to the antrum. Wall thickness 13 mm. There are enlarged lymph nodes in the area of the liver gate (GDS, group 12) up to 35 mm, as well as lymph nodes along the greater curvature of the stomach (group 3, 4). 04/12/10. conducted the first course of PCT according to the FOLFOX scheme. Moved satisfactorily. Hematological indicators are within normal limits. 05/05/05. the second course of chemotherapy was conducted according to a similar scheme. During the administration of chemotherapy side effects were not observed. Three weeks after the completion of two courses of PCT, with a control computed tomography of the abdominal organs, pronounced positive dynamics is observed in the form of a decrease in the diameter of the lymph nodes from 35 to 23 mm, from 15 mm to 8 mm. A decrease in the thickness of the wall of the stomach in the affected area from 13 to 8 mm is noted. June 4, 2010 the operation was performed: gastrectomy, splenectomy, cholecystectomy, lymph node dissection D2. The postoperative period was uneventful. Sutures were removed on the 14th day. The patient was discharged from the hospital in satisfactory condition. Postoperative histological examination No. 11586-635 / 10 of 06.16.10: low-grade adenocarcinoma with invasion of the entire wall and metastases of 22 l / node, III tbsp. therapeutic pathomorphosis. Three months later, during a follow-up examination of data for relapse, progression of the process was not obtained.

Example 2

Medical history No. 11509. Patient L., 69 years old, was in the department from 01/11/11. 01/01/11 with a diagnosis of cancer of the body of the stomach, subtotal lesion, stage III. 853-83 / 11 from 01/27/11: moderately differentiated adenocarcinoma with invasion of the entire wall thickness and ingrowth into the tissue, mts of 3 l / node from 14. During a CT scan (prior to chemotherapy), the tumor occupies the proximal part of the stomach to the middle thirds with dimensions 101 * 36 mm. By small curvature there are small l / nodes. Explicitly increased l / nodes in the abdominal cavity were not detected. 11.24.10 treatment was carried out according to the proposed method: the first course of PCT according to the FOLFOX scheme. Moved satisfactorily. Hematological indicators are within normal limits. 12/14/10. the second course of chemotherapy was conducted according to a similar scheme. During the administration of chemotherapy side effects were not observed. Three weeks after the completion of two courses of PCT, with a control computed tomography of the abdominal organs, pronounced positive dynamics is observed in the form of a decrease in the size of the tumor from 101 mm to 54 mm. No apparent enlarged l / nodes in the abdominal cavity

Thus, the application of the proposed method helps to reduce complications, improve long-term results of the combined treatment of patients with locally advanced gastric cancer, prevent the progression of the tumor process and distant metastasis.

Information sources:

1. Davydov M.I. Stomach cancer: what determines the standards of surgical treatment / M.I. Davydov, M.D. Ter-Ovanesov, A.N. Abdikhakimov, V.A. Marchuk // Practical Oncology: selected lectures / Ed. S.A. Tyulyandina, V.M. Moiseenko. - SPb .: Publishing house "Center TOMM", 2004. - S.473-83.

2. Zyryanov B.N., Afanasyev S.G., Zavyalov A.A., Musabaeva L.I. Intraoperative radiation therapy - Tomsk, 1999. - 286 p.

3. Kang S., Moon H., Sung J. // Phase II study of S-1 and irinotecan combination chemotherapy as a first-line therapy for patients with advanced gastric cancer. Korean Cancer Study Group Protocol ST05-02.

Claims (1)

A method for the combined treatment of locally advanced gastric cancer, including chemotherapy followed by a radical operation, characterized in that patients undergo two courses of systemic polychemotherapy (PCT) before surgery according to the FOLFOX 6 scheme Oxaliplatin - 85 mg / m ² 2-hour intravenous infusion in 1st day, Leucovorin - 200 mg / m ² 2-hour intravenous infusion on the 1st, 2nd day, 5-Fluorouracil - 400 mg / m ² intravenously streamally on the 1st day, then 5-fluorouracil - 2 , 4-3.0 g / m ² 46-hour intravenous infusion, a second course is carried out after 2-3 weeks .