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Efficacy of Doxorubicin and Docetaxel in Treatment of Metastatic Breast Cancer Appears Independent of Administration Schedule

Doxorubicin and docetaxel (DOC) both afford good therapeutic results in women with metastatic breast cancer independent of the schedule of administration, according to an Italian study.

According to Sara Cresta, MD, of the Department of Oncology, Istituto Nazionale Tumori, Milan, and colleagues, the best approach for the optimal application of non-cross-resistant drugs in treatment of metastatic breast cancer is undetermined. To test the respective merits and limits of different schedules of administration of doxorubicin and DOC, the researchers performed a phase 2 study rate of complete response in 123 breast cancer patients.

Patients were randomised to receive doxorubicin and DOC administered either as a combination (60 mg/m2 of each drug), or by alternating or sequential cycles of 4 for each drug (100 mg/m2 DOC and 75 mg/m2 doxorubicin). In addition, they were also randomised to antibiotic prophylaxis with oral ciprofloxacin, 500 mg twice daily from days 7 to 14 of each cycle, or no therapy to evaluate the prevention of febrile neutropaenia.

All patients received biochemistry assessments prior to each cycle and weekly complete blood cell counts. Left ventricular ejection fraction was assessed after a cumulative dose of doxorubicin of 300 mg/m2 and repeated before every cycle after reaching a cumulative dose of 400 mg/m2.

Overall, patients in each treatment group received a median of 8 cycles and a median relative dose intensity of greater than or equal to .9. The overall response in the combination, alternating and sequential schedules was 63%, 52% and 61%, respectively, and the corresponding rates of complete response were 15%, 14% and 11%, respectively.

Grade 4 neutropaenia (81%) was the most frequent adverse event in all treatment groups. Other grade 3/4 toxicities occurring in similar frequencies across groups included diarrhoea, nausea, vomiting and asthenia. Febrile neutropaenia and stomatitis occurred across treatment groups, but at a significantly higher incidence in patients receiving the combination regimen. Antibiotic prophylaxis did not prevent episodes of febrile neutropaenia or infection.

Toxicity caused delay of treatment in 16% of cycles in each treatment group and adverse events caused discontinuation of treatment in 11.5% of patients, including 7 in the combination group, 2 in the alternating group, and 5 in the sequential group.

Although results indicated that all 3 schedules are feasible and effective, the more pronounced toxicity of the combination regimen led the researchers to conclude that it was least favourable when treating women with metastatic breast cancer.

Aventis-Antony, France provided study funding.


Ann Oncol 2004 Mar;15:3:433-9. "A randomized phase II study of combination, alternating and sequential regimens of doxorubicin and docetaxel as first-line chemotherapy for women with metastatic breast cancer"

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