Correlation between experimentally and clinically demonstrated activity of two new cytotoxic agents in breast cancer

Experimental evidence of the cytotoxic activity of two new agents was obtained using five lines of human breast carcinoma serially transplanted into immunosuppressed mice. Tumor growth delay was used to compare the effect of the new agents with that of cytotoxic drugs of known value in human breast cancer. The mean specific growth delay (number of tumor volume doubling times saved) for each agent against the five lines was: CL232/315 (mitoxantrone) 1.9; M-AMSA (4'[9 - acridinyl] amino-methane sulphon - M - ansidine) 0.5; cyclophosphamide, 1.9; adriamycin, 1.8; melphalan 2.2. There was no significant difference between the activity of mitoxantrone and the clinically useful drugs, but m-AMSA (amsacrine) was significantly less active than the other agents. A clinical trial of mitoxantrone at the Royal Marsden Hospital has confirmed the prediction of useful activity against breast cancer. Objective responses (CR + PR, UICC response criteria) were noted in 21 out of 70 (30%) patients with advanced breast cancer treated with the drug. The responses were of 4-7 months plus duration, and the 30% response rate compares favorably with other single agents. Although amsacrine is active in many forms of malignant disease, several Phase II studies have shown it to have little effect in breast cancer. By using panels of xenografts of different tumor types, it should be possible to select the most appropriate human tumors against which to test a new cytotoxic agent in Phase II studies.