Gemcitabine plus doxorubicin as first-line treatment in advanced or metastatic breast cancer (MBC), a phase II study.

Introduction: Doxorubicin and Gemcitabine have promising antineoplastic activity and manageable toxicity as a single agent in the treatment of patients (pts) with advanced breast cancer.

Aim Of The Study: This study evaluated the efficacy and toxicity of the combination of gemcitabine plus doxorubicin as first-line treatment of advanced or MBC patients.

Patients And Methods: Patients with advanced or MBC received gemcitabine 1250mg/m2 IV on days 1 and 8 plus doxorubicin 60mg/m2 IV on day 1 every 21 days for a maximum of 6 cycles.

Results: Thirty-five patients were included, and all are evaluable for safety and efficacy. Median age was 47 years (range, 33 to 60 years). Fourteen patients (40%) were post-and 21 (60%) were premenopausal. Prior treatment included mastectomy (23pts); adjuvant nonanthracycline containing combination chemotherapy (18pts); adjuvant hormonal therapy (3pts) and 2 pts did not receive any adjuvant therapy. Twelve patients had metastatic disease at presentation. Seventeen pts were chemonaive. Hormonal receptors were positive in 6, negative in 21, and unknown in 8 pts. Site of metastasis included one site in 15 pts, two sites in 14, and three sites in 6 pts. Complete remission was observed in 6/35 (17.1%) and partial remission in 14/35 (40%) pts, for an overall response rate of 57.1%. Stable disease was observed in 8 (22.9%) and progressive disease in 7 (20%) pts. The median time to tumor progression was 7 months (range, 5-23 months; 95% CI, 6-8 months) and the median survival time was 16 months (range, 6-43 months; 95% CI, 13-19 months). The overall survival at 1 and 2 years was 74.2% and 34.2%; respectively; with 4/35 (11.4%) patients alive at 40 months. A total of 186 cycles of treatment were administered (range2-6 cycles, median 6 cycles). The doses of both doxorubicin and gemcitabine were modified after interim analysis of toxicity following the first 22 cycles administered to the first 10 patients [Mucositis grade 3-4 occurred in 6/10 (60%), grade 3-4 neutropenia in 3/10 (30%), and febrile neutropenia grade 3 in 2/10 (20%) patients] to doxorubicin 50mg/m2 on day 1 and gemcitabine to 1000 mg/m2 on days 1 and 8 in the remaining cycles. After doses reduction, the toxicity was generally tolerable.

Conclusion: The combination of gemcitabine plus doxorubicin after doses modification can be safely administered every 21 days with promising response as first-line therapy for MBC. The response rate, time to disease progression and overall survival rates of this regimen are comparable to other standard therapies for MBC, as well as other gemcitabine combinations.