Phase II trial of doxorubicin and paclitaxel plus granulocyte colony-stimulating factor in metastatic breast cancer: an Eastern Cooperative Oncology Group Study.
OBJECTIVE
Several groups have reported that the combination of doxorubicin plus paclitaxel given as a 3-hour intravenous (IV) infusion for up to eight cycles produces a high response rate (> 80%) and complete response rate (> 20%) in metastatic breast cancer, but is also complicated by a 20% incidence of congestive heart failure (CHF). The purpose of this phase II trial was to evaluate the antineoplastic activity of the regimen in a multi-institutional setting and to reduce the incidence of cardiotoxicity by limiting treatment to a maximum of six cycles.


METHODS
Fifty-two patients with advanced breast cancer received doxorubicin (60 mg/m(2) by IV injection) followed 15 minutes later by paclitaxel (200 mg/m(2) by IV infusion over 3 hours) every 3 weeks for four to six cycles.


RESULTS
Objective responses occurred in 25 of 48 assessable patients (52%; 95% confidence interval [CI], 38% to 66%), including four complete responses (8%; 95% CI, 0% to 16%). The median cumulative doxorubicin dose given was 240 mg/m(2) (range, 132 to 360 mg/m(2)). Eleven patients (21%) were documented as having a decrease in the LVEF below normal, including three patients (6%; 95% CI, 0% to 12%) who developed CHF.


CONCLUSIONS
The doxorubicin/paclitaxel regimen that we used is unlikely to produce an objective response rate of more than 70% and a complete response rate of more than 20% in patients with metastatic breast cancer, and proved to be excessively cardiotoxic for use in the adjuvant setting.
Sparano
J A
JA
Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Bronx, NY 10461-2373, USA.
Hu
P
P
Rao
R M
RM
Falkson
C I
CI
Wolff
A C
AC
Wood
W C
WC
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D017239:Paclitaxel