N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial.
BACKGROUND
Because of the single-agent activity of irinotecan hydrochloride, combination of irinotecan and docetaxel treatment against metastatic breast cancer (MBC) should be evaluated.


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/m(2)) and irinotecan (70 mg/m(2)) 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.
Tan
W W
WW
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL. Electronic address: tan.winston@mayo.edu.
Hillman
D W
DW
Division of Biostatistics, Mayo Clinic, Rochester, MN, USA.
Salim
M
M
Division of Hematology and Oncology, Allan Blair Cancer Center, Regina, Saskatchewan, Canada.
Northfelt
D W
DW
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ.
Anderson
D M
DM
Division of Hematology and Oncology, Abbott Northwestern Hospital, Minneapolis, MN.
Stella
P J
PJ
Department of Hematology and Oncology, Michigan Cancer Research Consortium, Ann Arbor, MI.
Niedringhaus
R
R
Department of Hematology and Oncology, Duluth CCOP, Duluth, MN.
Bernath
A M
AM
Department of Hematology and Oncology, Geisinger Clinic and Medical Center, Danville, PA.
Gamini
S S
SS
Department of Hematology and Oncology, Missouri Valley Cancer Consortium, Omaha, NE, USA.
Palmieri
F
F
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL.
Perez
E A
EA
Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D002166:Camptothecin