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

Purpose: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therap y with standard combination chemotherapy in metastatic breast cancer patien ts. Patients and Methods: A total of 365 women with measurable metastatic breas t cancer, previously untreated with chemotherapy for their metastatic disea se, were randomized to receive either immediate chemotherapy with cyclophos phamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, am onafide, carboplatin, or elsamitrucin, followed by CAF, Results: The toxicity of each single agent followed by CAF was comparable t o that of CAF alone. The cumulative response rates for the single agent fol lowed by CAF were not statistically different from those of CAF alone (44% v 52%; P = 24) However. in the multivariate analysis, patients with viscera l disease had a trend toward lower response rates on the phase II agent plu s CAF arm (P =.078). Although survival and response duration also were not statistically significantly different between the two study arms (P =.074 a nd P =.069, respectively), there was a suggestion of benefit for the CAF-on ly arm. Conclusion: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of respon se, 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 can cer. J Clin Oncol 17:1397-1406. (C) 1999 by American Society of Clinical On cology.