Method for predicting efficiency of autohemochemotherapy in patients with cancer of mouth cavitary and pharyngeal organs

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with biochemical trials in the field of oncology. Moreover, before the onset of autohemotherapy in patients one should detect the content of thyroid hormones -triiodothyronine and thyroxine, and hypophysial hormone - thyreotropin. At its value ranged 166-408 one should predict efficiency of therapy, and at coefficient value ranged 34-106 - the absence or low efficiency of therapy. The present method enables to detect sensitivity of tumor to autohemochemotherapy before its onset, avoid application of inefficient medicinal remedies and their possible toxic impact and prevent groundless expenses of expensive preparations.

EFFECT: higher efficiency and accuracy of prediction.

2 ex, 1 tbl

 

The invention relates to medicine, namely to biochemical research in Oncology, and can be used in the treatment of patients with cancer of the organs of the oral cavity and pharynx as a prognostic criterion for the effectiveness of chemotherapy treatment.

The response of the tumor to drug therapy due to complex, currently still poorly understood biochemical mechanisms underlying its sensitivity or resistance to specific chemotherapeutic agents. This greatly complicates the individualization of the treatment process. At the same time the possibility of obtaining information that allows you to start chemotherapy to predict the response of tumors at specific effect, is of great importance for the timely selection of an appropriate treatment strategy. In this regard, one of the important directions of research in the field of clinical Oncology is the development of methods for pre-treatment evaluation of tumour response plan cytostatic therapy.

There is a method of determining individual sensitivity of tumor and lymphoid tissue to chemotherapeutic drugs in vitro (copyright certificate №475532 from 07.03.75, bull. No. 24 30.06.75, Siskin GI, Borduchkov YU.N., Taradin L.V., Malyutina LI), based on a study by electron paramagnetic resonance dynamics of the free radicals in the tissue samples under the influence of pre-incubation with different doses of certain chemotherapy drugs and combinations of drugs. The disadvantage of this method is the need for a large number of definitions for the establishment of the effective doses and combinations of drugs using significant amounts of tumor tissue in the duration of the study.

There is a method of predicting the sensitivity of the mucous membrane of the oral cavity to drug therapy, selected as a prototype (Nagibin AA Cytoplasmic receptors for androgen, estrogen and hormonal status in patients with cancer and leukoplakia of the mucous membranes of the oral cavity. Amorf. Diss..., Ph.D.. M, 1988). The author's research found that malignant lesions of oral mucosa in 62% of cases have receptors both male and female sex steroid hormones (androgens and estrogens); 44,8% of tumors contain only the androgen receptor, and 34.4% - only the estrogen receptor. The number of receptors in all cases exceeded 10 fmol/mg protein, which according to the modern view is seen as necessary conditions for the development of the response of the tumor to the effects agnogenic hormones. Based on these data, the author considers it expedient to develop schemes of drug therapy this tumors with the use of hormonal and antihormonal drugs and use the quiet schemes for the treatment of patients, tumors which contain receptors for sex steroids. By definition, the author of Any received data can be used in two ways: 1) to identify hormonecontaining tumors and the appointment of adequate endocrine therapy; 2) for the purpose of diagnosis (abstract. Diss...KMN, 1988, p.7). In his study, the author generally does not deal with issues of chemotherapy cancer patients of this localization, but only emphasizes that revealed the presence of receptors androgenov and/or estrogens in tumors serves as a basis for development of further schemes endocrine (hormonal therapy (ibid p.6 - scientific and practical significance of the work). A limitation to this method of predicting the effectiveness of neoadjuvant therapy is its applicability solely to assess the antitumor action of hormonal preparations, whereas the response of the tumor to the introduction of drugs of other classes, in particular cisplatin, methotrexate and 5-perurail, the mechanism of action on tumor cells is not associated with steroid hormone receptors, may be independent of these parameters in nature. In this regard, the determination of steroid hormone receptors in tumors of the mucosa of the oral cavity can not be considered as a predictor effectively the ti neoadjuvant drug therapy, contains no hormonal or antihormonal drugs.

The aim of the invention is to determine the efficiency of autohemotherapy prior to its implementation.

This objective is achieved in that in patients before autohemotherapy treatment determined in the blood content of thyroid hormones - triiodothyronine, thyroxine, and pituitary hormone - tireotropina, determine the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina and when it is within 166-408 predict the effectiveness of treatment, and a value of the coefficient within 34-106 - no or low effectiveness of the treatment.

The invention: “a Method for predicting the effectiveness of autohemotherapy cancer patients organs of the oral cavity and pharynx” is new, because it is unknown the level of medicine in the field of biochemical research in Oncology as a prognostic criterion.

The novelty of the invention lies in the fact that in patients before treatment to determine the blood content of thyroid hormones - triiodothyronine and thyroxine and pituitary hormone tireotropina, calculate the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina and when it is within 166-408 predict effektivnostey, and when the value of the coefficient within 34-106 - no or low effectiveness of the treatment.

The approach used is to search for predictors of the efficacy of chemotherapy is determined by the fact that the neuroendocrine system is one of the main regulators of metabolic processes, thus stimulating interaction between the tumor and the body. Among hormonal indicators of particular interest are the thyroid hormones, which unlike other hormones control the main stages of all types of metabolism - protein, lipid, carbohydrate, and play a leading role in shaping the adaptive reactions of the organism.

The invention is industrially applicable as it can be used in health care, in medical institutions for the treatment of cancer patients, Oncology and oncologic dispensaries.

The invention of “a Method for predicting the effectiveness of autohemotherapy cancer patients organs of the oral cavity and pharynx” is as follows.

In patients with cancer of the mucous membranes of the oral cavity and pharynx with III (11%) and IV (in 89% of cases) stages of the disease before treatment was investigated serum triiodothyronine, thyroxine and tireotropina. Determination of hormone radioimmunoassay was performed using the standard test set of the firms in Immunotech (Czech Republic) and CIS-International (France). Calculate the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina. After the study, patients received a course of neoadjuvant autohemotherapy drugs cisplatin (100 mg/m2), methotrexate (50 mg/m2) and 5-fluorouracil (up to 5000 mg/m2with subsequent evaluation of the effectiveness of drug therapy according to the degree of regression of the tumor. In treated patients, regression of the tumor ranged from 0 to 100%, which indicates they have tumors in both sensitive and resistant to this type of cytostatic therapy. The results for the regression of the tumor were analyzed in accordance with the magnitude of the initial (before treatment) the ratio of the concentrations of triiodothyronine and thyroxine concentration tireotropina. It was found that 14 patients (73%), in which the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina averaged 277±38,84 with limits 166-408 neoadjuvant chemotherapy was accompanied by 50-100%regression of tumor. The other 8 patients (27%) the average value of the coefficient is equal to 61,82±10,75 with limits 34-106 - regression of the tumor in this group of patients ranged from 0 to 40% (table 1).

Table 1
Correlation of the degree of regression of the tumor under the influence of autohemotherapy with thyroid status of the patients before the treatment
The ratio T3+T4/TSHRegression of the tumor (in %)The number of observations
277±38,84 (166-408)50-100%14
61,82±10,75 (34-106)0-40%8

The results of the comparative analysis indicate that the background (before treatment) the value of the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina is an informative predictor of the sensitivity of the tumor to the scheme neoadjuvant autohemotherapy. Patients with the magnitude of the ratio of the sum of the concentrations of triiodothyronine. and thyroxine concentration tireotropina within 166-408, it is possible to predict the achievement of 50-100% regression of the tumor, and when the ratio is within 34-106 predicted no or weak effect that in such cases requires a possible reconsideration of the treatment regimen.

Examples.

Ave. 1. Patient E., 66 years old, IB. No. 5145/g was admitted to the Department of tumors of the head neck, RNII 9.04.02 was diagnosed with cancer of the mucous membrane of the floor of mouth with lymph node metastases sees both sides, T4N2M0st. IV, clinical group 4 (cytological analysis No. 9467-68 squamous cell carcinoma). Before treatment studied blood levels of triiodothyronine, thyroxine and tireotropina, it amounted to 0.87 nmol/l, 82,60 nmol/l and 2,20 μLU/1, respectively. The ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina equal 37,94.

10.04.02 the course of autohemotherapy scheme: day 1 - cisplatin 100 mg/m22nd day - methotrexate 50 mg/m2from 2 to 6 days and 5 fluorouracil 1000 mg/m2. 3 weeks after treatment evaluated the effectiveness of chemotherapy - regression of the tumor was 20-25%.

Thus, the low value of the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina (37,94) combined with a slight regression of the tumor under the influence of drugs, that is, a predictor of low efficiency of chemotherapy in this patient.

PR. Patient H., 62, IB. No. 16757/h, was admitted to the Department of tumors of the head neck, RNII 23.12.01 was diagnosed with cancer of the mucous membrane of the floor of mouth with metastases in the lymph nodes of the neck to the left, T3N2M0st. IVC, clinical group 2 (histological analysis No. 629886 squamous cell carcinoma). Before the blood triiodothyronine, thyroxine of tireotropina with the submitted 2.25 nmol/l, 126,4 nmol/l and 0.47 m LU/I, respectively. The ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina equal 273,72. With 25.12.01 a course of autohemotherapy scheme: day 1 - cisplatin 100 mg/m22nd day - methotrexate 50 mg/m2from 2 to 6 - days 5-fluorouracil 1000 mg/m2. Treatment the patient satisfactorily, without complications and side effects. 3 weeks after treatment evaluated the effect of autohemotherapy - regression of the growth amounted to 90%.

Thus, the high value of the ratio of the sum of the concentrations creationin and thyroxine concentration tireotropina (273,72) combined with a high degree of regression apocalypt vieniem drugs, that is, a predictor of high efficiency autohemotherapy.

Technical and economic efficiency “method of predicting the effectiveness of autohemotherapy cancer patients organs of the oral cavity and pharynx” is that the definition of efficiency autohemotherapy before its application allows to predict the effect of future treatment and, thus, will relieve the patient from inefficient stage of treatment and use of drugs with adverse (toxic) effects on the body allows an individual to plan the most efficient the tactics of cancer treatment.

A method for predicting the effectiveness of autohemotherapy cancer patients organs of the oral cavity and pharynx, including chemotherapy, biochemical study, characterized in that before the start of chemotherapy treatment in patients determine in the blood content of thyroid hormones - triiodothyronine, thyroxine, and pituitary hormone - tireotropina, determine the ratio of the sum of the concentrations of triiodothyronine and thyroxine concentration tireotropina and when it is within 166-408 predict the effectiveness of treatment, and when the value of the coefficient within 34-106 - no or low effectiveness of the treatment.



 

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