RU2255734C1 - Method for treating patients with locally metastasing forms of cancer at localization in mucosal area of pharyngeal oral department - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: the method deals with 2 courses of polychemotherapy at the first stage due to regional intra-arterial introduction of cisplatin at the dosage of 100 mg/m² during the first day of every course and 6-h-long intra-arterial infusion of 5-fluorouracil at total dose of 750 mg/m² in the morning since the 2^nd to the 6^th d of every course. Chemotherapy should be performed at the background of total magnetotherapy at frequency of magnetic field being 98-112 Hz, intensity of 25-30 oersted, duration of every seance being 30 min, the number of seances corresponds to the duration of chemotherapeutic courses. At the second stage in 2-3 wk after finishing chemotherapy it is necessary to conduct the course of distance radiation therapy (DRT) at multifractioning the dosage by SFD being 1.2 Gy twice daily 5 times weekly up to TFD being equivalent to TDF (time-dosage-fraction) of 62-70 Gy onto primary focus and 40-46 Gy onto areas of regional lymph outflow. As modifiers one should apply cisplatin during the first 2 wk of radiation therapy, hyperbaric oxygenation during the first 10 d of radiation therapy and total magnetotherapy since the 11^th d of DRT course till its ending. At the third stage in case of residual metastases in lymph nodes of patient's neck in 2-3 wk after the end of radiation therapy one should conduct operative interference in lymph outflow pathways. The method enables to decrease toxicity of chemo-and radiation therapy due to decreased radiation reactions, stimulation of immune system and improved microcirculation.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, namely to oncology, and can be used to treat patients with locally advanced forms of cancer of the mucous membrane of the oral cavity of the pharynx.

Known methods of treating patients with locally advanced forms of tumors of the mucous membrane of the oropharynx, including chemotherapy and radiation therapy in various combinations (Tumors of the head and neck. A.I. PACHES, M., Medicine, 1997, pp. 293-340).

However, the method is ineffective and causes a large number of complications.

The closest to the achieved positive result (prototype) is a method of treating patients with locally advanced forms of tumors of the oral cavity and oropharynx, including polychemotherapy, which consists in the intravenous administration of cisplatin 100 mg / m ² on the 1st day of treatment of each course, 5-fluorouracil in a dose of 1000 mg / m ² by means of a 120-hour infusion, in the second step combined treatment - radiotherapy with curative intent using rapid fractionation in the split mode, a summing the exact dose of 1 Gy (Gray) three times a day with an interfractional interval of four hours to the total focal dose (SOD) equivalent to 66-70 Gy (“Modern approaches to the treatment of oropharyngeal cancer.” I.A. GLADILINA, M.A. SHABANOV, Practical Oncology, vol. 4, No. 1, 2003).

However, when applying the known method there is a high frequency of complications of radiation therapy.

The authors propose a new effective method of treating patients with locally advanced forms of tumors of the oropharynx mucous membrane, which consists in a phased treatment: chemotherapy with general magnetotherapy, remote radiation therapy (DLT) with modification with platinum preparations, magnetotherapy and hyperbaric oxygenation (HBO) followed by surgical intervention on the pathways of lymph outflow in the presence of residual metastases in the lymph nodes of the neck.

A positive result of the proposed method is to increase the effectiveness of treatment by increasing the effectiveness of chemotherapy and radiation therapy, reducing the number of complications of radiation therapy.

A positive result is achieved by the fact that at the first stage of treatment, 2 courses of neoadjuvant intraarterial regional polychemotherapy (RCPT) are carried out using a modifying agent (general magnetotherapy): cisplatin (platamine) at a dose of 100 mg / m ² on the 1st day of treatment of each course, 5-fluorouracil in the form of a 6-hour infusion (time interval - morning hours) at a dose of 750 mg / m ² from day 2 to 6 of each course against the background of general magnetotherapy, at the second stage, a radical course of remote radiation therapy with non-traditional fractionation is carried out with daily fragmentation of the dose with a single focal dose (ROD) of 1.2 Gy twice a day with an interval of 4-6 hours (multifractionation or accelerated fractionation) with a continuous course with irradiation of the primary focus and areas of regional lymph outflow using radio modifiers and in the third stage they carry out an operative intervention on the pathways of lymph outflow in the presence of residual metastases in the lymph nodes of the neck.

The proposed method is as follows:

The treatment is carried out in stages:

- I stage - the patient is given 2 courses of chemotherapy against the background of magnetotherapy,

- Stage II - a radical course of remote radiation therapy with modification of platinum, magnetotherapy and HBO,

- Stage III - if necessary, surgical treatment in areas of regional metastasis (N 1-3).

The first stage of polychemotherapy involves the introduction of two drugs: cisplatin (platamine) at a dose of 100 mg / m ² against the background of hyperhydration on the first day of each course intraarterially, which is introduced through a catheter installed in one case into the superficial temporal artery, in another - through occipital artery. 5-fluorouracil at a dose of 750 mg / m ² is administered to the patient on days 2-6 of each course by a long 6-hour intra-arterial infusion. The time of administration (morning hours) is associated with the presence of a circadian rhythm in the concentration of 5-fluorouracil in the blood during prolonged infusions with the lowest concentration at 18 hours and the highest at 05 hours. The infusion is carried out using a dispenser of medicinal substances "LINEOMAT" (KARL-MARX-STADT).

Chemotherapy is carried out against the background of general magnetotherapy, the purpose of which, firstly, is to stimulate the immune system and, secondly, to improve microcirculation. The following parameters are used for this: magnetic field strength - 25-30 Oersted, magnetic field frequency 98-112 Hz. The shape of the magnetic field is a sinusoidal half-period. The duration of one session is 30 minutes. The number of sessions corresponds to the duration of the chemotherapy course. The main effect of this magnetotherapy regimen is to stimulate the bone marrow structures of the chest (spongy tissue), liver and spleen.

II stage. After chemotherapy is completed, 2-3 weeks after the relief of adverse reactions, patients undergo a radical course of remote radiation therapy (DLT) on the gamma-therapeutic complex “ROKUS-AM” without a scheduled break by the method of daily dose splitting (multifractionation) with a ROD of 1.2 Gy two once a day with an interval of 4-6 hours 5 times a week (daily dose of 2.4 Gy) with simultaneous irradiation of the primary lesion and areas of regional lymph outflow to SOD, equivalent to VDF 62-70 Gy for the primary lesion and 40-46 Gy for zones regional lymph outflow (with preventive purpose in the absence of metastases in the lymph nodes of the neck and with a preoperative goal in the presence of metastases on the neck) using platinum preparations (platamine, cisplatin) as modifiers during the first two weeks of radiation treatment (platamine 40 mg 2 times a week iv against the background of overhydration up to OD 160 mg), hyperbaric oxygenation (HBO) in the first 10 days in order to improve oxygenation of irradiated tissues (technique - compression 0 atm - 10 min, isopression 0.5 atm - 40 min, decompression 0.5 atm - 10 min), general magnetotherapy s to 11 days before course DLT closure radiotherapy for physiotherapy complex "MAGNITOR-AMP" in static magnetic field with a frequency of 120-128 Hz, a voltage of 10-15 oersteds, the shape of the magnetic field - a sinusoidal half cycle. The duration of one session of magnetotherapy is 30 minutes. The goal of general magnetotherapy during radiation therapy is to improve the microcirculation of irradiated tissues, reduce swelling of the mucous membranes of the oral cavity and oropharynx, which reduce local radiation reactions, stimulate the branches of the cervical nerve plexus.

III - stage: if necessary, 2-3 weeks after the end of radiation therapy, surgery is performed on the lymphatic outflow tract in the presence of residual metastases in the lymph nodes of the neck.

CLINICAL EXAMPLE 1

Patient AM SVETLOV, 53 years old, male, has been treated in the Department of Head and Neck Tumors since December 2002, medical history No. 21327.

DIAGNOSIS: Cancer of the mucous membrane of the oral cavity of the pharynx, left, IV art. T2N3M0.

G.D. No. 8357 of November 25, 2002 — squamous c-r without keratinization. The body area was 1.7 m ² .

Objectively, before the start of treatment, the patient had a ulcerous growth of the tumor, occupying the left palatine tonsil up to 2.5 cm in diameter, in the middle third of the neck on the left - an unplaced conglomerate of metastatic lymph nodes up to 7.5 cm in diameter.

December 20, 2002, the patient underwent catheterization of the external carotid artery from the left by access through the occipital artery. From 12/21/2002 to 01/01/2003, 1 course of intra-arterial regional chemotherapy was carried out: platinum 170 mg in 1 day at a time against hyperhydration (at the rate of 100 mg / m ² ), 5 - fluorouracil by prolonged six-hour infusion from the second to the sixth day with a total dose of 6.5 g at the rate of 750 mg / m ² .

01/13/2003, catheterization of the external carotid artery on the left by access through the superficial temporal artery on the left. From January 14, 2003 to January 23, 03, the 2nd course of regional polychemotherapy was carried out according to a similar program. The total doses of chemotherapy drugs received by the patient during the second course were the same as during the first course. Drug therapy was carried out against the background of general magnetotherapy in the mode of stimulating the immune system, improving microcirculation - magnetic field strength of 25-30 oersted, magnetic field frequency - 98-112 Hz.

After PCT, examination in the oropharynx of tumor growth was not determined. The effect of carrying out RPC on the primary lesion was 100%. In the middle third of the neck on the left after the end of the PCT course, a residual conglomerate of l / y up to 4 cm in diameter was determined (stabilization of the process). Complications of polychemotherapy in the form of alopecia, mucositis were noted. 3 weeks after the end of chemotherapy, the side effects stopped.

From February 12, 2003 to March 21, 2003, the patient underwent a radical course of remote radiation therapy without interruption at the gamma-therapeutic complex “ROKUS-AM” in static mode using a three-field irradiation technique with simultaneous irradiation of the primary focus and areas of regional lymph outflow according to the technique daily crushing of a daily dose (multifractionation) with a ROD of 1.2 Gy 2 times a day with an interval of 5 hours (daily dose of 2.4 Gy) daily up to a SOD of 62.2 Gy (which is equivalent to 60 Gy for VDF) to the primary focus and 42 G on the lymph nodes of the neck (preoperative onnaya dose).

Radio modification was carried out by applying a comprehensive technique:

- platamine in the first two weeks of treatment 40 mg intravenously 2 times a week against the background of hyperhydration to OD 160 mg;

- hyperbaric oxygenation in the first 10 days of the course of radiation therapy (technique - compression 0 atm - 10 minutes, isopression 0.5 atm - 40 minutes, decompression 0.5 atm - 10 minutes between sessions of radiation therapy);

- general magnetotherapy from the 11th day of the course of radiation therapy at the MAGNITOR-AMP physiotherapeutic complex in static mode with a magnetic field frequency of 120-128 Hz, a voltage of 10-15 oersteds, the shape of the magnetic field is a sinusoidal half-period.

The goal of general magnetotherapy during radiation therapy was to improve the microcirculation of irradiated tissues, reduce swelling of the mucous membranes of the oral cavity and oropharynx, which reduce local radiation reactions, stimulate the branches of the cervical nerve plexus.

After a course of radiation therapy, tumor growth in the oropharynx was not determined (complete regression), in the middle third of the neck on the left - residual l / y up to 2.5 cm in diameter (partial regression), the dose of DLT on which was 42 Gy.

COMPLICATIONS OF RADIATION THERAPY:

- dry epidermitis with hyperpigmentation of the skin in the irradiation zones;

- focal radioepithelitis on the mucous membranes of the oral cavity and oropharynx, mucositis. After 2.5 weeks, the complications of radiation therapy stopped.

April 14, 2003, the patient underwent surgery on the pathways of the lymph outflow (Crail operation). There were no postoperative complications, healing by primary intention.

Postoperative No. 1382 from 04/24/2003 - against the background of fibrosis - single cells belonging to c-r (therapeutic pathomorphosis of the III stage).

The proposed method treated 4 patients (4 men) aged 34 to 65 years. All patients had locally common forms of growth of tumors of the oral pharynx (T3N0M0-1, T2N1M0-1, T3N1M0-1, T2N3M0-1). All patients underwent 2 courses of RPXT according to the proposed scheme. Efficiency was: on the primary focus - complete regression of 75%, partial 25%. For metastases - complete regression was 33.3%, partial 66.6%. Patients underwent 8 courses of RCPT, during which the following complications were noted: nausea / vomiting - I-II degree - 4 courses, leukopenia I-II degree - 1 course, stomatitis - 6 courses, allopecia developed in 3 patients.

Thus, the overall effect of the courses of the studied chemotherapy program on the background of magnetotherapy for the primary lesion was 100%, for regional metastases - 100%, toxicity was lower than with standard courses of systemic PCT.

At the second stage of treatment, all patients received a course of remote radiation therapy according to the radical program using a multifraction technique of 1.2 Gy 2 times a day with an interval of 5 hours 5 times a week to total focal doses equivalent to 60-66 Gy depending on the prevalence of TNM with using platinum preparations as modifiers (platinum 40 mg 2 times a week in the first two weeks of DLT OD 160 mg), general magnetotherapy and HBO.

When conducting radiation therapy according to the proposed method, all patients experienced radiation reactions in the form of dry epidermitis in areas of hyperpigmented skin irradiation, the phenomena of radioepithelitis were focal in nature and stopped in the next 12-14 days without the use of corrective therapy. In no case did radiation complications cause a cessation or interruption in the course of radiation therapy. In no case were severe radiation complications observed in the form of confluent radioepithelitis or arrosive bleeding.

At the last stage of treatment, two patients with residual metastases to the lymph nodes of the neck underwent surgery on the lymphatic paths of the neck in the form of Crail surgery. There were no postoperative complications.

Thus, the method is highly effective and can be used in specialized oncological institutions involved in the complex treatment of patients with tumors of the oral pharynx.

Claims (1)

A method for the treatment of patients with locally advanced forms of cancer of the mucous membrane of the oral pharynx, which includes, at the first stage, conducting 2 courses of chemotherapy by regional intra-arterial administration of cisplatin at a dose of 100 mg / m ² on the first day of each course and a 6-hour intra-arterial infusion of 5-fluorouracil in a total dose of 750 mg / m ² in the morning, from 2 to 6 days of each course chemotherapy is carried out against the overall magnetotherapy with a frequency 98-112 Hz magnetic field, intensity 25-30 Oe, a session duration of 30 minutes, number of treatments with tvetstvuet duration of chemotherapy; at the second stage, 2-3 weeks after the end of chemotherapy, a course of remote radiation therapy (DLT) is conducted with multifractionation of a dose of 1.2 Gy twice a day 5 times a week to an SOD equivalent to VDF (time-dose-fraction) 62 -70 Gy for the primary lesion and 40-46 Gy for the regions of regional lymphatic drainage, using cisplatin as modifiers in the first two weeks of radiation treatment, hyperbaric oxygenation in the first 10 days of radiation therapy and general magnetotherapy from day 11 of the course of DLT to its end; in the third stage, in the presence of residual metastases in the lymph nodes of the neck, 2-3 weeks after the end of radiation therapy, surgery is performed on the pathways of the lymph outflow.