Adriblastina (Doxorubicin) - Breast Cancer [antikvár]

ADRIAMYCIN IN BREAST CANCER Even if in advanced and/or metastatic breast cancers high response rates are reported for single agents - and especially for ADR alone - it is today generally accepted that combination chemotherapy is the most active treatment. Many combinations have been evaluated, ADR containing polychemothe-rapies appearing to be the most active. Presently, a "plateau" has been reached. 50% significant objective responses being commonly obtained (10-20% compitte responses). Single institutions experiences give a top of 70-80% response rate in pilot or highly selective trials. The most active combinations now widely used, due to their easy and simple design and to good tolerance, are reported in the following Table. Cancer Chemother. Pharmacol. 1, 35-39 (1978) Cancer C hemotherapy and Pharmacology © by Springer-Verlag 1978 Original Papers Sequential Combination Chemotherapy in Advanced Breast Cancer Cristina Brambilla, Pinuccia Valagussa, and Gianni Bonadonna Istituto Nazionale Tumori, Milan 20133, Italy Summary. The results of a prospective controlled study with alternating cycles of two effective non-cross resistant combinations in advanced breast cancer are reported. The two combinations consisted of adriamycin plus vincristine (A V) and cyclophosphamide, methotrexate and fluorouracil (CMF). The study was carried out with the main intent to obtain a higher incidence and a longer duration of response compared to that obtained with either combination alone. A total of 110 évaluable patients (55 for each treatment group) not previously treated with chemotherapy were randomly allocated to receive either Therapy A (2 AV followed by 2 CMF) or Therapy B (2 CMF followed by 2 AV). Complete plus partial response (53% vs 60%) as well as duration of remission (11 vi 12 months) were similar in both treatment groups. At the lime of present analysis, 20patients died from cancer (Therapy A: 9; Therapy B: 11) and in 9 of them death occurred during the first 12 months. The administration of sequential combinations was no more toxic than the administration of either combination alone. Introduction Disseminated breast cancer is responsive to many tliera-peutic modalities. However, major advances have been recently achieved using multiple drug regimens. From 50—75% of patients respond to combination chemotherapy and this high response rate has made a favorable impact upon survival. However, different combinations when given alone have reached a plateau in their capac- Presented inpart at the 68th Annual Meeting of the American Association for Cancer Research, May 18-21, 1977, Denver, CO Supported in part by Contract No. NOl-CM-33714, with DOT, NCI, NIH Reprint requests should be addressed to: G. Bonadonna, M.D., Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, Italy ity to control advanced breast cancer [5, 8]. Therefore, new approaches must be considered, namely the use of new drugs, the addition of hormone or immunotherapy as well as the administration of non-cross resistant combinations. The present study was undertaken with the intent to increase both the incidence and the duration of response by alternating two non cross resistant combinations. In fact, it is theoretically conceivable that improved results could be obtained by exposing an heterogeneous population of neoplastic cells to various agents having different mechanisms of action. The combinations selected were AV (adriamycin and vincristine) and CMF (cyclophosphamide, methotrexate and fluorouracil) which were shown in a previous controlled study to be equally effective and non-cross resistant upon primary chemotherapy failure [71. Since the initial tumor regression could aflfect the duration of remission, we have decided to randomize our series to investigate, on a controlled basis, the optimal sequence schedule. In fact, we have observed in our previous trial [7] that the tumor regression was more rapidly induced by AV compared to CMF. In particular, at the level of soft tissue lesions, after 2 cycles of treatment, 58% of women started on AV were already in g5od partial remission compared to 38% of those given CMF. Patients and Methods Drug Treatment Patients not previously treated with chemotherapy and with measurable lesions were randomly allocated to receive either Therapy A: 2 cycles of AV followed by 2 cycles of CMF, or Therapy B: 2 cycles of CMF followed by 2 cycles of AV. The alternating treatment was continued until progression of disease or for 6 additional cycles after the achievement of complete remission. If patients remained in complete remission after additional chemotherapy, no further treatment was given. In patients still responding to treatment and who had reached a total dose of 550 mg/m^ of adriamycin, therapy was con- 0344-5704/78/0001/0035/$ 01.00