A randomised attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization

Human breast cancer cells in tissue culture can be growth inhibited by tamoxifen, an inhibition that can be reversed by estrogen. The question of whether tamoxifen inhibition of breast cancer followed by es-tradiol reversal would increase the efficacy of chemo-therapy was asked. One hundred ten patients were prospectively randomized to chemotherapy consisting of cytoxan (750 mg/m 2) and Adriamycin (30 mg/m 2) on day 1 plus 5-fluorouracil (5-FU) (500 mg/m 2) and methotrexate (MTX, 40 mg/m 2) on day 8 versus the same chemotherapy plus tamoxifen (20 mg/m2) on days 2-6 and premarin (0.625 mg every 12 hours for three days) on day 7. Chemotherapy was given in 21-day cycles. The first 55 patients were randomized to a regimen in which 5-FU preceded MTX by 24 hours; thereafter, all patients received MTX followed in one MULTIPLE proposals have been made in the past few years to increase the efficacy of chemotherapy. A considerable body of evi-dence ' 2 has suggested that an apparent plateau-ing of response rates (in the range of 55%-65%) and of median duration of response (generally less than one year) has occurred in advanced breast cancer treatment. Most efforts to improve therapeutic effectiveness by increasing dose in-tensity, ' by using "noncross-resistant " drugs,4 or by using more drugs ' have been unsuccessful. While a small minority of patients treated with cytotoxic chemotherapy may achieve a complete remission with a longer associated response du-ration, the eventual relapse and death of virtually all of these patients suggests that drugs alone have not yet been able to eradicate sufficient numbers of tumor cells to result in cure of more than an occasional patient. Given the general safety and palliative poten