Treatment of Metastatic Breast Cancer with Cyclophosphamide, Methotrexate, Vincristine and Fluorouracil.

Abstract

From November 1970 to June 1972, 55 patients with metastatic breast cancer were treated with a 4-drug combination (cyclophosphamide, Methotrexate, vincristine and fluorouracil) administered intravenously over a 5-day period (table 1). Treatment was repeated after a 2-week interval for the first 3 cycles, then after 4 weeks. Six more patients were incompletely treated but found evaluable for the toxicity study. The great majority of cases (51/55) was pretreated with radiotherapy, hormone and/or chemotherapy (table 3). The overall response rate was 69 %. Complete (CR) plus partial (PR) remissions (> 50 %) were 46 %. From this evaluation bone lesions was arbitrarily not included since recalcification occurs rarely after chemotherapy. The medium duration of CR was 8 months, that of PR 4 months (table 4). The most responsive lesions were those localized in the soft parts (75%) followed by metastases to lung (55%), pleura and liver (40%). Recalcification of bone lesions was observed in 17 % of cases (table 6). The number of cycles required to produce a regression was found proportional to the degree of response, with a mean of 2 cycles to obtain a PR and a mean of 3 cycles to obtain a CR (table 7). The longest regression was seen in patients with lung or liver involvement (table 8). The duration of the free interval was a positively correlated with the type of response (table 9). The dose limiting factor was represented by bone marrow depression which often required a dose attenuation schedule (table 10 and 11). The actuarial analysis of survival curves (fig.1) showed that patients achieving CR+PR lived longer than those with static disease or progression during combination chemotherapy (P < 0.05). It is concluded that combination chemotherapy can prolong the survival of responsive patients with metastatic breast cancer. The most effective combination can be found only through appropriate controlled clinical trials.