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 02, 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: 2575 years [43% < 50 years; 57% ³
50 years]) were entered42% with stage IIIB and 58% with stage
IV breast cancer. Of the stage IV patients, 33% had received prior
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 515. 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: 416 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.