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Safety and Efficacy of Using a Single Agent or a Phase II Agent Before Instituting Standard Combination Chemotherapy in Previously Untreated Metastatic Breast Cancer Patients: Report of a Randomized Study—Cancer and Leukemia Group B 8642

From the Department of Medicine, University of Massachusetts Medical School, Worcester, MA; Walter Reed Army Medical Center, Washington, DC; Uniformed Services University of the Health Sciences, Bethesda, MD; University of California, San Francisco, CA; Memorial Sloan-Kettering Cancer Center, New York, NY; Duke University Medical Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Emory University School of Medicine, Atlanta, GA; Dartmouth Medical School, Cotton Cancer Center, Lebanon, NH; and Cancer and Leukemia Group B, Chicago, IL.

Address reprint requests to Mary E. Costanza, MD, Department of Medicine, Division of Hematology Oncology, University of Massachusetts Medical Center, 55 Lake Ave North, Worcester, MA 01655; email mary.costanza{at}banyan.ummed.edu

PURPOSE: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients.

PATIENTS AND METHODS: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF.

RESULTS: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm.

CONCLUSION: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.

The contents of this article are solely the responsibility of the authors and do not necessarily reflect the official views of the National Cancer Institute.

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