Adriamycin in Combination and in Combined Treatment Modalities.

Abstract

The paper reviews the current strategic approach of the Istituto Nazionale Tumori of Milan with adriamycin (ADM) in combination with other drugs as well as in combined treatment modalities for various neoplasias of adults and children. The preliminary results obtained during the past four years in malignant lymphomas, acute leukemias, carcinoma of the breast, and neuroblastoma are reported. With the exception of the group of malignant lymphomas treated with a quintuple drug regimen (MABOP), none of the patients admitted the different trials had received chemotherapy. Most studies were controlled with random allocation to two different combinations. Cross over was carried out on relapse. In advanced Hodgkin's disease, non-Hodgkin's lymphomas, mammary carcinoma, soft tissue sarcomas, embryonal carcinoma of testicle, ovarian carcinoma, and multiple myeloma the main purpose of the study was to develop two independent non cross resistant combinations to be used sequentially in subsequent trials. There is a preliminary evidence that this is being obtained in Hodgkin's disease (ABVD vs. MOPP), in non Hodgkin's lymphomas (ABP vs. CVP) and carcinoma of the breast (ADM + VCR vs. CMF). In the other groups the patients were too few to permit conclusions. In acute lymphoblastic leukemia, in the leukemic phase of non-Hodgkin's lymphomas as well as in the group of solid tumors of children, combination chemotherapy and combined treatment modalities were not designed in a controlled fashion. ADM was introduced in all treatments because of its definite activity when employed as a single agent in refractory disease. Few therapeutic results are as yet available since most studies were started in 1974. However, the remission rate observed in the limited group of acute leukemias treated with ADM + VCR + prednisone is worth noting. The wide spectrum of activity of ADM justifies its use in several protocols of combination chemotherapy and in combined treatment modalities. With both full and reduced regimens drug tolerance was good, and in practically all studies more than 80 % of the optimal dose of ADM could be administered. All trials were properly designed to avoid a total dose of ADM exceeding 550–600 mg/m2 since cardiomyopathy (reversible) was observed in 2 patients after 600 mg/m2.