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Failure of Higher-Dose Paclitaxel to Improve Outcome in Patients With Metastatic Breast Cancer: Cancer and Leukemia Group B Trial 9342

From Dana-Farber/Partners Cancer Care, Boston, MA; State University of New York Upstate Medical University, Syracuse; Mount Sinai School of Medicine; Weill Medical College of Cornell University; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Chicago Medical Center, Chicago, IL; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO; Cancer and Leukemia Group B Statistical Center; Duke University Medical Center, Durham; University of North Carolina at Chapel Hill, Chapel Hill; Wake Forest University School of Medicine, Winston-Salem, NC; University of California San Francisco Cancer Center, San Francisco, CA; and Vermont Cancer Center, Burlington, VT.

Address reprint requests to Eric Winer, MD, Dana-Farber Cancer Institute, 44 Binney St, D1210, Boston, MA 02115; e-mail: ewiner{at}partners.org

PURPOSE: Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer.

PATIENTS AND METHODS: Four hundred seventy-four women with metastatic breast cancer who had received one or no prior chemotherapy regimens were randomly assigned to one of three paclitaxel dosing regimens—175 mg/m², 210 mg/m², or 250 mg/m²—each administered as a 3-hour infusion every 3 weeks. Women completed self-administered quality of life and symptom assessment questionnaires at baseline and after three cycles of treatment.

RESULTS: No evidence of a significant dose-response relationship was demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21% for the three regimens, respectively. A marginally significant association (P = .04) was seen between dose and time to progression; however, in a multivariate analysis, the difference was even less apparent. No statistically significant difference was seen in survival. Neurotoxicity and hematologic toxicity were more severe on the higher dose arms. There was no significant difference in quality of life on the three arms.

CONCLUSION: Higher doses of paclitaxel administered as a 3-hour infusion to women with metastatic breast cancer did not improve response rate, survival, or quality of life. There was a slight improvement in time to progression with higher dose therapy, which was offset by greater toxicity. When a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m² should be considered the optimal dose.

Supported in part by National Cancer Institute Grants CA32291 (E.W. and A.K.), CA33601 (D.A.B.), CA21060 (S.W. and J.A.K.), CA47577 (L.N.H.), CA04457 (R.A.M.), CA41287 (G.F.F.), CA12046 (M.C.P.), CA47559 (M.L.G.), CA03927 (S.A.S.), CA07968 (R.K.), CA60138 (I.C.H.), CA77651 (C.H. and L.N.), and CA77406 (H.M.).

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

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

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