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

Abstract

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 I11 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/mz 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% months respectively. Patients receiving adriamycin had significantly superior survival from the 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 doselimiting 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. URING THE PAST SEVERAL YEARS, THE ing search for new chemotherapeutic agents D Southwest Cancer Chemotherapy Study active in advanced refractory breast carcinoma.Group (SWG) has been involved in a continu-In one of our first studies, utilizing the intra-

Mitoxantrone as first-line chemotherapy in advanced breast cancer: results of a collaborative European study

“…In previously untreated patients Hoogstraten et al (11) reportcd a response to doxorubicin of 50% with a median duration of 8 months compared to 18+ months in the present study. Response rates of 38'}0 and 39% have been reported by others (12,13) with median response durations of 7.5 and 5.0 months, respectively. In a small randomized trial comparing doxorubicin and mitoxantrone in patients previously untreated with cytotoxic agents no significant difference was observed in response rates (40% vs 27%) and rcsponse durations (84 vs 96 days) (14).…”

Phase II Studies

“…The overall response rate for menogaril in this study was 19o70, less than the rate for single agent doxorubicin which is 28-43% in previously untreated patients [7,8]. Similar response rates to menogaril have been published by other authors.…”

Combination chemotherapy with adriamycin andcis-diamminedichloroplatinum in patients with neoplastic diseases

“…Thus, only one out of six patients responded, whereas a 38% response rate to adriamycin alone has been reported in a population of previously treated breast cancer patients. 4 No a.dvantage for combination chemotherapy ol adriamycin and DDP was recognizable in ovarian cancer, since aclriamycin alone has been reported to show activity in 25% and DDP alone has shown 227,b response rate in previously treated ovarian cancer T h u s , either could have accounted for the one response seen in the five patients treated.…”