Phase II Trial of Doxorubicin and Docetaxel for Locally Advanced and Metastatic Breast Cancer: Preliminary Results From NSABP BP-57

Based on results from phase I studies, one of the recommended doses for doxorubicin/docetaxel (Taxotere) is doxorubicin 60 mg/m² plus docetaxel 60 mg/m² every 21 days. However, information on the efficacy and toxicity of this dose level in breast cancer is limited. In preparation for a major adjuvant breast cancer study (NSABP B-30) in which doxorubicin/docetaxel would be used, we conducted a pilot phase II trial using this regimen at 14 NSABP (National Surgical Adjuvant Breast and Bowel Project) institutions.

Eligibility requirements included stage IIIB/IV breast cancer with measurable disease, performance status 0–2, normal left ventricular ejection fraction, and no prior chemotherapy (with the exception of nontaxane adjuvant chemotherapy, if completed more than 12 months before entry and if cumulative doxorubicin was £ 240 mg/m²). From July 1998 through July 1999, 89 patients (age range: 25–75 years [43% < 50 years; 57% ³ 50 years]) were entered—42% with stage IIIB and 58% with stage IV breast cancer. Of the stage IV patients, 33% had received prior adjuvant chemotherapy.

Doxorubicin/docetaxel was administered intravenously every 21 days with oral dexamethasone 8 mg bid for six doses and prophylactic oral ciprofloxacin 500 mg bid days 5–15. Growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia. When the cumulative doxorubicin dose reached 480 mg/m², patients could continue with docetaxel 100 mg/m² alone.

A total of 73 patients and 380 courses (mean: 5.2 cycles per patient) were evaluable for toxicity. Median time on study was 10 months (range: 4–16 months). Febrile neutropenia occurred in 29 patients (40%): 18 in the absence of growth factor support, and 11 despite prophylactic growth factor. One patient died from sepsis. Other grade 3/4 toxicities were nausea (3%), vomiting (3%), stomatitis (10%), diarrhea (5%), arthralgia/myalgia (3%), fluid retention (1%), pulmonary embolism (1%), and cerebrovascular accident (1%). Clinical congestive heart failure was seen in 2 patients (3%), both of whom had received cumulative doxorubicin to the 480-mg/m2 level. To date, 47 patients are evaluable for best response: there has been complete response in 3 patients (6%), partial response in 22 (47%), and stable disease in 15 (32%).

CONCLUSION: Doxorubicin/docetaxel with primary ciprofloxacin and secondary growth-factor prophylaxis is a well-tolerated and active regimen in breast cancer. Its value in the adjuvant setting is currently under investigation for patients with node-negative (ECOG 2197) and node-positive (NSABP B-30) breast cancer.

Click here for Dr. Gabriel N. Hortobagyi’s commentary on this abstract.