Annals of Oncology Advance Access published online on July 22, 2009
Annals of Oncology, doi:10.1093/annonc/mdp328
N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial
1 Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL
2 Division of Biostatistics, Mayo Clinic, Rochester, MN, USA
3 Division of Hematology and Oncology, Allan Blair Cancer Center, Regina, Saskatchewan, Canada
4 Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ
5 Division of Hematology and Oncology, Abbott Northwestern Hospital, Minneapolis, MN
6 Department of Hematology and Oncology, Michigan Cancer Research Consortium, Ann Arbor, MI
7 Department of Hematology and Oncology, Duluth CCOP, Duluth, MN
8 Department of Hematology and Oncology, Geisinger Clinic and Medical Center, Danville, PA
9 Department of Hematology and Oncology, Missouri Valley Cancer Consortium, Omaha, NE, USA
* Correspondence to: Dr W. W. Tan, Division of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Tel: +1-904-953-6153; Fax: +1-904-953-0984; E-mail: tan.winston{at}mayo.edu
Background: Because of the single-agent activity of irinotecan hydrochloride, combination of irinotecan and docetaxel treatment against metastatic breast cancer (MBC) should be evaluated.
Patients and methods: Single-stage phase 2 study of irinotecan and docetaxel to evaluate tumor response, toxicity, time to progression, and overall survival was carried out. Regimen of docetaxel (25 mg/m2) and irinotecan (70 mg/m2) was administered on days 1 and 8 of each 3-week cycle. Patients had histologically confirmed breast adenocarcinoma and metastatic cancer measurable with RECIST.
Results: Of 70 patients enrolled, 64 were assessable. Prior treatment with an anthracycline and a taxane was required. Eighteen (28%) patients [95% confidence interval (CI) 15% to 31%] had tumor response, plus four patients had stable disease (less than 30% decrease in sum of longest diameter and less than 20% increase) for >6 months. The clinical benefit rate was 34% overall. Median duration of tumor response was 6.7 months (95% CI 4.2–37.7 months); median follow-up was 18.6 months (range 8.5–37.7 months). The most common severe adverse events included fatigue [n = 16 (25%)] and neutropenia [n = 13 (20%)].
Conclusions: Weekly dosing of combination of irinotecan and docetaxel is active against MBC. However, the response rate to our regimen was not significantly better than single-agent docetaxel. Other schedules of irinotecan plus docetaxel should be considered for future studies.
adenocarcinoma, breast neoplasms, drug therapy, neoplasm metastasis
Received for publication October 7, 2008. Revision received May 12, 2009. Accepted for publication May 14, 2009.