Oral Irinotecan Regimen Active in Heavily Pretreated Metastatic Breast Cancer

TYLER, TEXAS-A 5-daycourse of oral irinotecan (Camptosar)given every 3 weeks is active in patientswith metastatic breast cancerafter the failure of prior anthracycline,taxane, and capecitabine (Xeloda) regimens,Svetislava J. Vukelja, MD, reported(abstract 562). Dr. Vukelja ofthe Tyler Cancer Center, in Tyler, Texas,presented results of a phase II studyof a 5-day, 60 mg/m²/day irinotecanregimen vs a 14-day, 30 mg/m²/dayschedule."Oral irinotecan offers patients convenienceand provides protracted drugexposure. Following reported activityof IV irinotecan in refractory metastaticbreast cancer, this study evaluatesefficacy and safety of two oralirinotecan schedules after failure ofprior anthracycline (A), taxane (T),and capecitabine (C)," Dr. Vukeljasaid.Primary EndpointsThe primary study objective was todetermine the confirmed objective responserate of single-agent oral irinotecanin this population. Secondaryendpoints were response duration,time to tumor progression, overallsurvival, and safety.Inclusion criteria were histologicallyconfirmed, measurable metastaticbreast cancer and failure of prior A, T,or C regimens (progression during orfollowing treatment, lack of responseafter four cycles, or significant treatment-related toxicity). Patients wererandomized to receive oral irinotecanat 60 mg/m² on days 1-5 (Dx5), repeatingevery 21 days, or 30 mg/m² ondays 1-14 (Dx14), repeating every 21days.Acceptable Safety ProfileAt the time of this report, 84 of 87patients on the 5-day arm and 39 of 40patients on the 14-day arm were evaluablefor response. The confirmed responserate (complete plus partial responses)was 14.3% on the 5-day regimenand 7.7% on the 14-day regimen.The 5-day arm had an acceptablesafety profile. Grade 3/4 drug-relatedadverse events included diarrhea(27.6% grade 3), fatigue (13.8% grade3, 1.1% grade 4), neutropenia (10.3%grade 3, 2.3% grade 4), and vomiting(12.6% grade 3, 0% grade 4). Drugrelatedadverse events resulted in hospitalizationin 9.2% of patients but nodeaths.The 14-day regimen was less welltolerated. There were five treatmentrelateddeaths (septic shock, renal failure)and higher rates of grade 3/4 diarrhea(42.4% grade 3, 7.5% grade 4)and hospitalization due to drug-relatedadverse events (27.5%)."Oral irinotecan is active in heavilypretreated patients with metastaticbreast cancer after failure of prior treatmentwith anthracycline, taxane, andcapecitabine (median five prior regimens).Overall response rate was 14%for the 5-day schedule and 8% for the14-day schedule. The 5-day dosingschedule appears to be better toleratedthan the 14-day schedule."