RU2164094C1 - Method of treating locally expanded mouth cavity cancer - Google Patents

Abstract

FIELD: oncological stomatology. SUBSTANCE: when performing chemotherapy, cis- platinum, methotrexate, and phthoruracilum are injected intravenously with autolymph after preliminary incubation for 30 min at 37 C with 200 ml of autolymph each. 6 h later, the same volume of autolymph with chemical preparations is injected intravenously. EFFECT: enhanced treatment efficiency. 2 cl, 2 ex

Description

 The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with cancer of the oral cavity with a primary local lesion or a relapse process. These patients are not subject to surgical or radiation treatment due to either the primary prevalence of the process, accompanied by erosion of large vessels, or the recurrent nature of the tumor, when all methods of specific treatment have been exhausted. As a rule, such patients are toxic, with severe hematological disorders. Therefore, a reduction in toxicity from the use of polychemotherapy with platinum preparations, which is the only way to prolong the life of patients, is necessary.

A known method of treating cancer of the oral cavity (see in the book. "Antitumor chemotherapy" under the editorship of N. N. Perevodchikova, M., "Medicine", 1986, p. 38) by intravenous administration of various combinations of chemotherapeutic agents. With inoperable or non-radically removed tumors, as well as with relapses of cancer, an intravenous administration scheme is used:
methotrexate 120 mg / m ² iv, + leucovarin, day 1;
cisplatin 100 mg / m ² iv, day 2;
fluorouracil 1000 mg / m ² iv, infusion for 2-6 days.

 3 cycles are carried out with an interval of 21 days.

 However, the effectiveness of using this and similar schemes for locally advanced inoperable oral cancer does not exceed 30-40% according to the authors, and the percentage of complete regression ranges from 0 to 5. At the same time, remission lasts an average of 11 months. The second significant drawback of the use of chemotherapy regimens, including platinum preparations, is their high toxicity. So nausea and vomiting occur in almost 100% of patients, droperidol, frenolone, seduxen are used to stop them, but their effectiveness is not always achievable. Platinum drugs affect all three sprouts of hematopoiesis: leukopenia occurs in 50%, anemia - in 40% of patients. Nephro- and ototoxicity in the treatment with platinum drugs occurs in 30% of patients. Impaired renal function is associated with damage to the tubules and is manifested by an increase in the level of urea, creatinine and uric acid in biochemical blood tests. Ototoxicity is the result of a defeat of the VIII pair of cranial nerves and is manifested in the form of transient tinnits and hearing loss.

 The treatment of these complications is laborious and expensive.

A known method of treating inoperable forms of oral cancer (Karaseva. V.V. "Combined chemotherapy of squamous cell carcinoma of the oral cavity and oropharynx." Auth. Diss. .. Doct. Medical Science. Tomsk, 1997), including intravenous administration:
cisplatin 100 mg / m ² in 1 day against the background of overhydration;
5-fluorouracil 1000 mg / m ² day from 1 to 5 day in the form of a 120-hour continuous infusion ;.

methotrexate 7 mg / m ² from 1 to 5 days of treatment at a time.

 Then, all patients underwent remote gamma therapy in SOD 58-60 Gy.

However, the effectiveness of this method of treating locally advanced oral cancer is only 64.4%, of which full regression took place in 33.3% and partial tumor regression in 31.1%. The stabilization of the process was recorded in 28.9%, and progression - about 7% of cases. In this case, pronounced side effects were observed:
hematological - leukopenia in 42.8%; anemia in 9.9%;
thrombocytopenia in 9.1%;
gastroenterological - nausea / vomiting in 49.3%; diarrhea in 18.7%;
stomatitis in 11.8%; hepatotoxicity in 11.8%; (increase in aminotransferase levels); renal - 16.8%.

 The aim of the present invention is to improve the immediate results of the treatment of patients with locally advanced oral cancer.

The goal was achieved in that patients with oral cancer T ₄ N _x M _o drained the thoracic duct, collected lymph, then polychemotherapy was performed according to the following scheme:
methotrexate 50 mg / m ² incubated in 200 ml autolymph at a temperature of 37 ^o C for 30 min, intravenously, on the first day;
cisplatin 100 mg / m ² , incubated in 200 ml autolymph at a temperature of 37 ^o C for 30 min, intravenously, against the background of hyperhydration (standard) on the second day;
5-fluorouracil 750 mg / m ² incubated in 200 ml autolymph at a temperature of 37 ^o C for 30 minutes, intravenously from the second to the sixth day.

 To reduce the toxicity of chemotherapy drugs, especially cisplatin, 6 hours after administration of chemotherapy drugs with autolymph, 200 ml of autolymph without chemotherapy was intravenously administered.

 All patients underwent 3 similar courses of autolymphochemotherapy, alternating the administration of chemotherapy on autolymph and autolymph without chemotherapy.

 The invention is new, since it is not known from the level of medicine in the field of oncology in the treatment of locally advanced cancer of the oral cavity with chemotherapeutic agents. The novelty of the invention lies in the fact that in the treatment of inoperable forms of cancer of the oral cavity, chemotherapeutic agents are administered on the patient's autolymph, alternating the administration of chemotherapeutic drugs dissolved in lymph with the introduction of pure autolymph.

 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.

 The use of autolymph as a medium for dissolving and administering chemotherapy determines the combination of their specific antitumor activity with additional nonspecific stimulation of the immune system caused by cellular elements of the lymph.

 In accessible sources of information from Russia, the CIS countries and abroad, indications of a similar method for improving the immediate results of treatment of locally common forms of oral cancer with a simultaneous objective reduction of toxic side effects of chemotherapeutic agents were not found.

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

 To prove this, we provide extracts from case histories confirming the clinical effect of treatment by the proposed method.

 Example 1. Patient B., born in 1952, case history No. 1634 / k, was admitted to the maxillofacial department of the Rostov Cancer Research Institute with a diagnosis of larynopharynx cancer with metastases to the lymph nodes of the neck of St III gr. 4, pharyngostomy.

 On 1.03.99, an advanced extirpation of the larynx with pharyngeal resection was performed. Histological analysis of N 527597-598-squamous cell carcinoma with keratinization. From March 22, 1999 to April 19, 1999, and from April 26, 1999 to May 20, 1999, the patient received a course of distance gamma therapy up to a total focal dose of 60 Gy.

 In September 1999, the patient again entered the maxillofacial department of the RNII with a fixed motionless conglomerate of lymph nodes on the left neck, severe pain, stopping only with the use of narcotic analgesics.

 September 15, 1999, the patient underwent drainage of the thoracic lymphatic duct.

From September 16, 1999 to October 4, 1999, he was given a course of autolympho-chemotherapy using the proposed method according to the following scheme:
September 16, 1999 - 50 mg of methotrexate, previously incubated for 30 minutes at a temperature of 37 ^o C with 200 ml of autolymph, was intravenously administered. After 6 hours, 200 ml of autolymph was intravenously administered.

September 17, 1999 - after standard hyperhydration, 100 mg of cisplatin was introduced intravenously, previously incubated for 30 min at a temperature of 37 ^° C with 200 ml of autolymph. After 6 hours, 200 ml of autolymph was intravenously administered.

From September 20 to September 24, 1999, 1000 mg of 5-fluorouracil, previously incubated for 30 minutes at 37 ^° C with 200 ml of autolymph, was intravenously administered. Daily, 6 hours after administration of the chemotherapy drug, 200 ml of autolymph was intravenously administered.

 During the course of autolymphochemotherapy, the patient did not show any of the toxic side effects of cytostatics.

 Biochemical blood parameters, see table. 1.

 After the course of autolymphochemotherapy, a significant mobility of the conglomerate of the lymph nodes appeared, the pain syndrome decreased significantly, the patient stopped receiving narcotic analgesics, noted a marked improvement in the general condition (lack of weakness, full sleep and appetite). 10.10.99, the patient was able to perform Crail surgery on the left (the operation was performed radically).

 Currently, the patient lives without signs of relapse and metastases.

Example 2. Patient A., born in 1941, medical history No. 9792 / k, was admitted to the maxillofacial department of the Rostov Cancer Research Institute with a diagnosis of oral mucosa of the oral cavity St III gr. 4. Histological analysis N 60482-487 from 10.25.99, - squamous cell carcinoma. From October 27 to November 3, 1999, the patient underwent a course of autolymphochemotherapy with the proposed method according to the following scheme:
10.27.9999 - 50. mg of methotrexate, previously incubated for 30 minutes at a temperature of 37 ^o C with 200 ml of autolymph, was administered intravenously. After 6 hours, 200 ml of autolymph was intravenously administered.

October 28, 1999 - 100 mg of cisplatin was introduced intravenously, previously incubated for 30 minutes at a temperature of 37 ^o C with 200 ml of autolymph. After 6 hours, 200 ml of autolymph was intravenously administered.

October 29, November 1-4, 1999 - 1000 mg of 5-fluorouracil, previously incubated for 30 minutes at a temperature of 37 ^° C with 200 ml of autolymph, was intravenously administered. After 6 hours, 200 ml of autolymph was administered intravenously daily.

 Biochemical blood parameters, see table. 2.

 The patient was discharged home for a planned break in treatment. November 29, 1999, he again entered the maxillofacial department of the RNII for the second course of autolymphochemotherapy. When examining a patient, a tumor was not found. Histological analysis N 551849-850 from 11.29.99, - no tumor was found in the delivered material. In this case, 100% tumor regression was recorded.

The proposed method was carried out treatment of 16 patients with cancer of the oral cavity. In this case, there were adverse reactions that were unexpressed and did not require additional funds for their relief:
hematological - leukopenia up to 3 thousand cells - 18.8%; anemia -12.5%; thrombocytopenia - 6.2%; gastroenterological - nausea / vomiting - 50%: diarrhea - was not; stomatitis - 6.2%, hepatotoxicity - was not (increase in aminotransferases); nephrotoxicity - was not.

 The effectiveness of the proposed method for the treatment of locally advanced oral cancer was 81.2% (13 people), of which 50% (8 people) had a complete regression and in 31.2% a partial regression of the tumor. The stabilization of the process is registered in 18.8%. The progression of the process was not detected in any case.

 The improvement of treatment results seems to us to be a combination of various positive factors consisting in increasing the antitumor activity of chemotherapy drugs after their preliminary incubation with autolymph, against the background of objectively reduced indicators of their toxic effect, especially cisplatin, as well as activation of antioxidant factors in the cells of the immunocompetent system under the influence of autolymph.

 The technical result from the use of the "Method of treating locally advanced oral cancer using platinum preparations" is that patients undergo this procedure without complications.

Claims (1)

A method of treating locally advanced oral cancer, including the use of platinum preparations, characterized in that during chemotherapy according to standard regimens, cisplatin, methotrexate and 5-fluorouracil are administered intravenously, pre-incubating them for 30 minutes at a temperature of 37 ^o C with 200 ml of autolymph each, and 6 hours after administration of chemotherapy with autolymph, intravenous administration of the same amount of autolymph without chemotherapy is carried out.

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