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Phase III Study of N,N-Diethyl-2-[4-(Phenylmethyl) Phenoxy]Ethanamine (BMS-217380-01) Combined With Doxorubicin Versus Doxorubicin Alone in Metastatic/Recurrent Breast Cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19

From the National Cancer Institute of Canada Clinical Trials Group, Ontario, Canada; Bristol-Myers Squibb International Corp, Wallingford, CT

Address reprint requests to Lesley Seymour, MD, National Cancer Institute of Canada Clinical Trials Group, Cancer Research Institute, Queens University, 10 Stuart St, Kingston, Ontario, Canada K7L3N6; e-mail: lseymour{at}ctg.queensu.ca.

PURPOSE: N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE; tesmilifene) is a novel agent that augments chemotherapy cytotoxicity in vitro and in vivo. A phase II trial combining DPPE and doxorubicin (DOX) in metastatic breast carcinoma showed increased response over that expected with DOX. We report a phase III trial comparing DOX with DPPE plus DOX in metastatic or recurrent breast cancer.

PATIENTS AND METHODS: Anthracycline-naive women with measurable metastatic disease were randomly assigned to receive, every 21 days, either DOX 60 mg/m² intravenously or DOX during the last 20 minutes of an 80-minute infusion of DPPE (5.3 mg/kg), in both cases to cumulative DOX doses of 450 mg/m². Patients receiving DPPE were aggressively premedicated to ameliorate toxicity. End points included progression-free survival (PFS), response rate (RR), and response duration (RD), quality of life (QOL), toxicity, and overall survival (OS).

RESULTS: A planned interim analysis failed to detect an RR difference more than 5%. The study was closed to additional accrual and all DPPE was discontinued. The final analysis was conducted as planned after 256 progression events (median follow-up, 20.5 months). There was no significant difference in RR, RD, or PFS between arms. DPPE plus DOX was statistically superior to DOX in OS (hazard ratio, 0.66; 95% CI, 0.48 to 0.91; P = .021). DPPE plus DOX was associated with more gastrointestinal and CNS toxicity. No consistent influence on QOL was detected.

CONCLUSION: This study demonstrated no advantage in RR, RD, or PFS but significantly superior OS for DPPE plus DOX. Additional studies of DPPE are warranted.

Supported by the National Cancer Institute of Canada Clinical Trials Group and Bristol-Myers Squibb.

Presented at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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