Superiority of adriamycin over oral nitrosoureas in patients with advanced breast carcinoma.A southwest cancer chemotherapy study group study

In a continuing search for agents effective in advanced breast cancer, nonrandomized studies by the Southwest Cancer Chemotherapy Study Group have shown a 29% response rate with BCNU, a 19% response rate with CCNU, and a 36% response rate with adriamycin. Following these leads, a randomized Phase III study has compared adriamycin (60–75 mg/m2 intravenously every 3 weeks) with the oral nitrosoureas, CCNU (100–130 mg/m2 orally every 6 weeks) and methyl CCNU (125–150 mg/m2 orally every 6 weeks) in patients with advanced breast cancer, all of whom had already failed in at least one trial with conventional chemotherapeutic agents. The patients' age, menopausal status, sites of metastatic involvement, and extent of prior therapy were nearly identical in the three treatment groups. Ten inevaluable patients died within the first 2 weeks from tumor. For the remaining 100 patients, the response rate was: adriamycin 15/40 (38%); CCNU 4/20 (14%); and methyl CCNU 1/31 (3%). The median durations of response for adriamycin, CCNU, and methyl CCNU were 7, 3, and 1 1/2 months respectively. Patients receiving adriamycin had significantly superior survival from die start of chemotherapy, and the duration of survival of adriamycin responders (12+ months) was significantly superior (P <.001) to adriamycin non-responders (5 months). Metastatic lesions responding to adriamycin included skin and soft tissue (46% response rate), lungs (36%), liver (20%), and bones (19%) compared with only soft tissue and skin responses (12%) with the nitrosoureas. Myelosuppression was the dose-limiting toxicity with all three regimens, but was less prominent with methyl CCNU, suggesting that the dose of this agent could have been higher. An exploration of adriamycin in patients without prior chemotherapy is presently ongoing, with a response rate that is currently in excess of 50% and equal to the response rate of a control population receiving a commonly used five-drug combination regimen. Adriamycin is an effective new agent in the therapy of breast cancer, and combination trials seem indicated.