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Randomized Phase II Study of Two Irinotecan Schedules for Patients With Metastatic Breast Cancer Refractory to an Anthracycline, a Taxane, or Both

From the Mayo Clinic and Mayo Foundation, Jacksonville, FL; Mayo Clinic, Rochester; Duluth Community Clinical Oncology Program (CCOP), Duluth, MN; Missouri Valley Cancer Consortium, Omaha, NE; Scottsdale CCOP, Scottsdale, AZ; Carle Cancer Center CCOP, Urbana; Illinois Oncology Research Association CCOP, Peoria, IL; Ochsner CCOP, New Orleans, LA; and Wichita HCCOP, Wichita, KS

Address reprint requests to Edith A. Perez, MD, Division of Hematology/Oncology, Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: perez.edith{at}mayo.edu

PURPOSE: A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules.

PATIENTS AND METHODS: MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m² weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m² every 3 weeks.

RESULTS: The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm.

CONCLUSION: Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.

Conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and supported in part by Public Health Service grants CA-25224, CA-35103, CA-35113, CA-35195, CA-35267, CA-35269, CA-35272, CA-35415, CA-35431, CA-37404, CA-37417, CA-52352, CA-60276, CA-63848, and CA-63849 from the National Cancer Institute, US Department of Health and Human Services, Bethesda, MD. Irinotecan and loperamide were supplied by Pharmacia & Upjohn, Peapack, NJ, now Pfizer Inc, New York, NY.

Preliminary results from this study were presented in an abstract for the 38th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

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

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