COMPARATIVE CHARACTERISTICS OF THE METHODS OF CHEMODRUGS ADMINISTRATION IN THE TREATMENT OF PATIENTS WITH LOCALLY-ADVANCED BREAST CANCER

Abstract

The development of new methods of treating patients with breast cancer (BC) causes no doubts at anyone at present moment. The statistical data testify to steady growth of BC sickness rate during recent 20 years without tendency to stabilization The special attention is paid to the development of new methods of treating BC patients (regional forms of disease) with unfavorable factors for forecast of tumor growth. The presented methods of treatment of patients with locally-advanced breast cancer consist in giving complex treatment using two simultaneous ways of administration of chemodrugs - selective intra-arterial and endolymphatic in combination with a systemic one. The results obtained demonstrated greater efficacy of treatment with combinations of selective intra-arterial chemotherapy with a systemic one compared with endolymphatic chemotherapy in combination with the systemic one for the treatment of this disease. Materials and methods. The present study was based on the data of 285 patients with locally-advanced forms of breast cancer HER/2-neu positive and basal-like biological subtypes, with the stages T4N0-2M0, the treatment was given in Donetsk regional antitumor center and Odessa University Clinic in 2000-2014. During the research for an adequate analysis of the results of treatment by the technique under consideration there were formed two groups of patients. The first investigated group included 221 patients, in 168 patients were diagnosed HER/2-neu positive tumors in immunohistochemical conclusion and 53 patients had basal-like biological subtype of the tumor. The program of the comprehensive treatment of patients in this group included the internal thoracic artery catheterization through the upper epigastric artery, two or three cycles of SIAPCT in combination with intravenous one with an interval of 21 days, evaluation of the effect of radiation therapy (RT) on the breast and zone of the regional lymph outflow in the static mode SFD- 2-2.5 Gy, CFD- 40 Gy, the interval, estimation of the effect. Mastectomy in the patients of the investigated group was performed only when there was a complete or partial tumor response (136 surgeries in a radical scope). Courses of intraarterial PCT were given in continuous long-term infusion (4 hours) by the scheme CMF, CAF or CAMF. Taking into account the possibility of local complications against the background of administration of some chemotherapeutic agents (most often - doxorubicin), half of the drug dose was administered intravenously. The total course doses of chemodrugs were calculated according to BSA criteria. The control group included 64 patients, 45 were identified to have HER/2-neu positive and 19 basal-like subtypes of breast cancer. The program of comprehensive treatment of the patients of this group includes endolymphatic chemotherapy according to the method developed by Donetsk regional antitumor center. As the main method of administration of chemodrugs in the lymphatic system there was used infusion introduction with the help of the system for intravenous drip, infusion rate was 0.3-0.5 ml/min that allowed us to exclude the possibility of extravasation of the chemodrug solution. The course dose of the drug was administered endolymphatically within 5-7 days. At the interval of 21 days two or three courses of ELPHT were given combined with the intravenous administration of anthracyclines (at the end of each cycle the catheter was removed, the catheterization was performed repeatedly). Then the effectiveness of the treatment by the criteria of RECIST was evaluated. Radiation therapy (RT) to the breast and area of the regional lymph outflow was given in a static mode SFD- 2-2.5 Gy, CFD- 40 Gy followed by evaluation of the effect. Mastectomy in the patients of the control group was performed only at the complete or partial tumor response (36 operations in a radical scope). Courses of endolymphatic PCT were given by the continuous long-term infusion (up to 8 hours) scheme of CMF, CAF or CAMF. Taking into account the possibility of local complications against the background of introduction of some chemotherapeutic agents, intercalator doxorubicin was administered intravenously, and antimetabolites and alkylating agents (methotrexate, 5-fluorouracil and cyclophosphamide) in all schemes were introduced endolymphatically. Results. The average life expectancy of patients of the investigated group was 3.43 ± 0.18 years, while in the control group it was 2.82 ± 0.3 that significantly exceeded the statistical data of domestic and foreign authors. Indices of total 3-year survival rate of patients of the investigated group were 59.9 ±4.5% and 5-year- - 43.1 ±5.5 months. In the control group indices of cumulative 3- and 5-year survival rates were significantly lower - 37.8% ± 6.6 and 25.2 ± 7.0%months respectively. Conclusions. 1. The results of complex treatment of locally-advanced breast cancer with unfavorable prognostic factors of tumor growth by the developed technique by using a combination of selective intra-arterial injection and intravenous chemotherapy in a pool of the internal thoracic artery in combination with radiation and hormonal therapy exceed the results of standard treatment programs for the patients with locally-advanced breast cancer with performing mastectomy and systemic chemotherapy. 2. The method developed by the authors can be recommended for widespread use in these patients.