A Phase II Randomized Study of Doxorubicin Alternated With Docetaxel vs Sequential Administration of Four Cycles of Docetaxel Followed by Four Cycles of Doxorubicin as First-Line Chemotherapy in Metastatic Breast Cancer Patients

August 2, 2000

From March 1996 to March 1998, 106 patients with untreated metastatic breast cancer (MBC) were treated with docetaxel (Taxotere) (100 mg/m²) and doxorubicin (75 mg/m²) on an alternating cycle-by-cycle (doxorubicin, docetaxel, doxorubicin, etc) or sequential (four cycles of docetaxel, then four cycles of doxorubicin) basis, every 3 weeks, for a maximum of eight cycles.

 

From March 1996 to March 1998, 106 patients with untreated metastatic breast cancer (MBC) were treated with docetaxel (Taxotere) (100 mg/m²) and doxorubicin (75 mg/m²) on an alternating cycle-by-cycle (doxorubicin, docetaxel, doxorubicin, etc) or sequential (four cycles of docetaxel, then four cycles of doxorubicin) basis, every 3 weeks, for a maximum of eight cycles.

Eligible patients included those with measurable MBC, less than 75 years old, with a World Health Organization (WHO) performance status (PS) of 0–2, no prior chemotherapy (CT) for MBC (prior adjuvant allowed provided < 240 mg/m² of prior doxorubicin), and adequate hematologic, renal, hepatic, and baseline left ventricular ejection fraction. Patient characteristics were well balanced: median age, 55 years (range: 29–75 years); median PS, 1 (range: 0–2). Adjuvant CT was received by 88% of patients (with anthracycline in 3 patients). Tumor characteristics for both arms (alternating/sequential) were as follows: viscera (82%/80%), liver (47%/54%), bone (39%/51%), and more than two organs (43%/40%).

The median number of cycles administered was 8 in both arms. Febrile neutropenia and grade 3 infection were observed in 18% (alternating) and 13% (sequential) of patients. With the exception of stomatitis (more frequent and more severe with alternating therapy), no other nonhematologic severe or grade 3/4 adverse events were observed. With a median follow-up time of 14 months and a median cumulative dose of 300 mg/m² of doxorubicin, no congestive heart failure was observed. Fluid retention was severe in only 1 patient. Activity was similar between alternating and sequential therapy: overall response rate, 60% (alternating)/67% (sequential); complete response, 2%/7%; liver response rate, 59%/62%; response duration, 47 wk/44 wk; time to progression, 39 wk/38 wk. As of March 1999, median survival was not yet reached in both arms.

CONCLUSION: Alternating and sequential administrations of doxorubicin and docetaxel are safe, feasible, and effective regimens. A comparison of alternating or sequential administration of doxorubicin and docetaxel with doxorubicin/docetaxel in combination is warranted.

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