Life-Threatening Sepsis Associated With Adjuvant Doxorubicin Plus Docetaxel for Intermediate-Risk Breast Cancer

CONTEXT Adjuvant chemotherapy with new cytotoxic agents for breast cancer must be properly assessed for toxicity. OBJECTIVE To describe adverse events associated with adjuvant chemotherapy for breast cancer, which led to premature termination of a clinical trial. DESIGN, SETTING, AND PATIENTS We conducted a prospective randomized multicenter study (Reposant sur des Arguments Pronostiques et Prédictifs [RAPP]-01) to compare the effectiveness of 2 chemotherapy regimens. Patients (women aged 18-70 years) had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes (≤3) or no positive axillary lymph nodes (N0), but were at a high risk of relapse. Patients were treated at 11 French cancer referral centers from June 1999 through January 2003. Primary prophylaxis for febrile neutropenia was not recommended in the study protocol. INTERVENTIONS Doxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2, or doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, given postoperatively for 4 courses. MAIN OUTCOME MEASURES The main end point was the disease-free survival rate at 5 years, as estimated using the Kaplan-Meier product limit method. Secondary end points included safety, which is the focus of this article, and overall survival. RESULTS A total of 627 women were enrolled. Median follow-up is currently too short (24 months) to analyze the primary end point. The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of perforative peritonitis occurred among patients with febrile neutropenia, all in the doxorubicin-docetaxel group. The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen (40.8%) than with the doxorubicin-cyclophosphamide regimen (7.1%) (P