RU2353359C2 - Method of neoadjuvant chemoradiotherapy in patients suffering from thoracic esophagus cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology and to be used for neoadjuvant chemoradiotherapy in the patients suffering from thoracic oesophagus cancer. Said therapy is ensured by introduction of cisplatin and leucovorin, and continuous intravenous infusions of fluorouracil dosed 300 mg/m². Cisplatin solution is introduced intravenously drop-by-drop and dosed 6 mg/m² daily once a day within 1 hour. Leucovorin is injected intravenously jet-like and dosed 30 mg/m². Radiotherapy involves daily fractions 3 Gy to total basic dose 30 Gy. The course dose of fluorouracil is 3600 mg/m², of cisplatin is 72 mg/m², of leucovorin 360 mg/m². Chemotherapy and radiotherapy are to be started the same day.

EFFECT: disclosed method allows for considerably reduced toxicity of treatment to be continuous, treatment of the patients originally of bad performance status, for doubly reduced time of neoadjuvant treatment with maintaining high clinical effectiveness.

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Description

The invention relates to medicine, namely to the combined use of chemotherapy and radiation therapy, and is intended to enhance the antitumor effects of radiation therapy in neoadjuvant mode in patients with cancer of the thoracic esophagus.

Increased resectability in patients with cancer of the thoracic esophagus and an attempt to improve long-term results contribute to the emergence of new antitumor combinations, including through a combination of radiation therapy and chemotherapy.

The basis for choosing a chemotherapy regimen in combination with radiation therapy was two works from Japan [1, 2], in which high direct results of treatment with low toxicity due to prolonged administration of cytostatics were presented. The authors administered the neoadjuvant drug 5-fluorouracil in the form of a continuous infusion at a dose of 250 mg / m ² , cisplatin 5 mg / m ² 1 hour before radiation therapy, leucovorin 30 mg / m ² . Then, radiation therapy was performed on the esophagus 2 Gy per day in a total dose of 40 Gy.

However, this method of chemoradiation treatment has several disadvantages. Firstly, radiation therapy in the traditional fractionation regimen at a dose of 40 Gy for 4 weeks, followed by a break in treatment for 2-3 weeks, necessary for stopping radiation reactions, is quite long in time (about 6-7 weeks), which requires additional costs for hospitalization and postpones the timing of surgical treatment. Secondly, prolonged administration of cytostatics throughout this period is difficult for patients to tolerate, which significantly reduces the quality of life.

The aim of the invention is to reduce toxicity, as a result, the possibility of treatment in patients in poor general status (Karnowski index = 70%); reduction of treatment time; terms of hospitalization while maintaining high treatment effectiveness.

This goal is achieved by introducing a fractionation regimen of radiation therapy in a total dose of 30 Gy to 3 Gy per fraction 5 times a week for 2 weeks and by reducing the duration of treatment to 3 weeks, increasing doses of cytostatics administered daily: cisplatin 6 mg / m ² , fluorouracil in a dose of 300 mg / m ² , leucovorin 30 mg / m ² .

The specified combination and sequence of distinctive actions are not known and do not follow explicitly from the existing level of science and technology, therefore, the claimed method corresponds to the inventive step.

The method is as follows.

After examination in order to clarify the stage of the disease and obtain morphological confirmation of cancer of the thoracic esophagus, before treatment, all patients undergo Seldinger catheterization of the subclavian vein. A continuous (round-the-clock), long-term (throughout the entire course of remote radiation therapy) intravenous administration of fluorouracil at a dose of 300 mg / m ² per day using an infusion pump begins. The course dose is 3600 mg / m ² . In parallel with the introduction of fluorouracil, once a day, daily, intravenously, for 1 hour, cisplatin 6 mg / m ² per 400 ml of 0.9% saline is administered. The course dose is 72 mg / m ² . Once a day, daily (before radiotherapy), leucovorin 30 mg / m ² is injected intravenously, jet for 3-5 minutes. The course dose is 360 mg / m ² . Chemotherapy and external radiation therapy begin on the same day. Within 30-60 minutes after the end of the administration of cytostatics, all patients receive remote radiation therapy to the thoracic esophagus, paraesophageal tissue and mediastinal lymph nodes with a single focal dose of 3 Gy, 5 times a week to a total focal dose of 30 Gy. 7-10 days after the end of treatment, a control examination is performed and surgical treatment is performed in the amount of subtotal resection of the esophagus. The total period of neoadjuvant treatment is 21-24 days.

The indicated treatment was carried out by us in 27 patients with cancer of the thoracic esophagus, who underwent simultaneous chemoradiotherapy in the neoadjuvant mode of the proposed method, due to which all patients received treatment in full, without interruption, there were no toxic reactions of the third degree. Reducing toxicity made it possible to conduct treatment in some patients with the Karnowski index = 70%. The treatment time was reduced from 6-7 weeks to 3 weeks. The immediate effectiveness of the treatment was 70.4%, taking into account the stabilization of the tumor process - 100%.

We present clinical examples of the use of the method.

Example 1. Patient P., 63 years old, clinical diagnosis: Cancer of the middle third of the thoracic esophagus T3N0M0 IIA Art. Dysphagia III Art. The histological conclusion is squamous cell carcinoma of a moderate degree of differentiation. According to the examination, the length of the tumor along the esophagus was 3 cm, the soft tissue component during x-ray examination was 2.5 cm. As a neoadjuvant chemoradiation treatment, the patient underwent radiation therapy in a total OD of 30 Gy, and cytostatics were infused in parallel: cisplatin 6 mg / m ² , leucovorin 30 mg / m ^{2 in a} bolus, fluorouracil at a dose of 300 mg / m ² in the form of a continuous infusion throughout the entire duration of radiation therapy (12 days). Complications - nausea of the II degree. 7 days after the end of chemoradiotherapy, a control x-ray and endoscopic examination was performed, which did not reveal the presence of a tumor in the esophagus. After another 3 days, the patient underwent subtotal resection of the esophagus with the simultaneous formation of an esophageal-gastric anastomosis on the neck. The histological conclusion is therapeutic pathomorphosis of the fourth degree. The patient was discharged in satisfactory condition.

Example 2. Patient W., 52 years old, clinical diagnosis: Cancer of the middle and lower third of the thoracic esophagus T3N0M0 IIA Art. Dysphagia II Art. The histological conclusion is squamous cell carcinoma of a moderate degree of differentiation. According to the survey, the length of the tumor along the esophagus was 5 cm, the soft tissue component during the X-ray examination was 3 cm. As a neoadjuvant chemoradiation treatment, the patient underwent radiation therapy in a total OD of 30 Gy, and cytostatics were infused in parallel: cisplatin 6 mg / m ² , leucovorin 30 mg / m ² bolus, fluorouracil at a dose of 300 mg / m ² in the form of a continuous infusion throughout the duration of radiation therapy (12 days). Complications - nausea of the I degree. 7 days after the end of chemoradiotherapy, a control examination was performed, which revealed a tumor resorption of 80%. After 3 days, the patient underwent subtotal resection of the esophagus with the simultaneous formation of an esophageal-gastric anastomosis on the neck. The histological conclusion is therapeutic pathomorphosis of the fourth degree. The patient was discharged in good condition home.

Thus, the inventive method can significantly reduce the toxicity of treatment and complete the planned treatment volume for all patients without interruption, makes it possible to treat patients in an initially poor general status (Karnovsky index = 70%); leads to a twofold reduction in the time of neoadjuvant treatment while maintaining high immediate efficacy of therapy.

Literature

1. Shimoyama S, Aoki F, Kojima J, Kaminishi M. A case of complete response to esophageal cancer by a novel concurrent chemoradiation therapy. Hepatogastroenterology. 1999 Jul-Aug; 46 (28): 2409-13.

2. Itoh Y, Fuwa N, Matsumoto A, et al. Concurrent chemoradiotherapy using protracted infusion about low-dose CDDP and 5-FU and radiotherapy for esophageal cancer. Nippon-Igaku-Hoshasen-Gakkai-Zasshi. 1999 Jul; 59 (8): 395-401.

Claims (1)

A method of neoadjuvant chemoradiotherapy in patients with cancer of the thoracic esophagus, including the introduction of cisplatin and fluorouracil, characterized in that it is additionally administered leucovorin, while the fluorouracil solution is administered intravenously infusion around the clock at a dose of 300 mg / m ² , the cisplatin solution is administered at a dose of 6 mg / m ² daily once daily intravenously for 1 h, and leucovorin is administered in a dose of 30 mg / m ² intravenous bolus injection, radiotherapy is performed on 3 Gy fractions daily to a total dose of 30 Gy, focal, and course dose ft ruratsila is 3600 mg / m ² cisplatin 72 mg / m ² leucovorin 360 mg / m ^2, chemotherapy and radiation therapy is started on the same day.