Publication Year: 2000 Visited: 72

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Phase II Trial of Weekly Docetaxel (Taxotere) Alone or in Combination with Trastuzumab (Herceptin) in Patients with Metastatic Breast Cancer. Ummekalsoom Malik, Joseph A. Sparano, Jane Manalo, Lakshmi Rajdev, Catherine Sarta, Una Hopkins, Susan Fineberg, Albert Einstein Comprehensive Cancer Center/Montefiore Med Ctr, Bronx, NY.

Weekly taxane therapy produces less myelosuppression and offers the potential for greater synergy with the anti-Her2 monoclonal antibody Herceptin, and docetaxel is the only taxane known to truly synergize with Herceptin in vitro (Semin Oncol 26 [Suppl 9]: 32-36, 1999) Objectives/Methods: The objective of this study was initially to determine the efficacy of intravenous docetaxel (33 mg/M2 over 1 hour) in metastatic breast cancer given on a continuous weekly basis without planned treatment holidays, and was later modified to evaluate weekly docetaxel plus Herceptin (4 mg/kg, then 2 mg/kg IV) in patients with Her-2 overexpressing tumors (2+ or 3+ by the DAKO Herceptest). Results: patient characteristics: N=25; median age 54 years; > 3 disease sites (9 [36%]); failed > 1 prior chemo for metastases (22 [88%]) including either paclitaxel (6 [24%]) or docetaxel (8 [32%]) every 3 weeks for metastases. Results: Partial response occurred in 9 of 22 evaluable patients (41%), including 4 of 16 patients (25%) treated with docetaxel alone, 5 of 6 patients treated with docetaxel and Herceptin, and 4 of 10 patients (40%) treated with docetaxel alone who had no prior docetaxel for metastases. Patients received a median of 8 treatments (range 1-44) over 8 weeks (range 1-49), resulting in a median dose intensity of 33 mg/M2/week (range 25-33 mg/M2/week). Toxicity consisted of grade 1-2 lacrimation in 11 (44%), fatigue in 9 (36%), nail changes in 7 (28%), and fluid retention in 6 (24%). Grade 3-4 toxicites included hyperglycemia (N=4), granulocytopenia (N=4), neuropathy (N=2), mucositis (N=2), anemia (N=2), and infection (N=1). Conclusions: These results are consistent with a previous report regarding weekly docetaxel with planned treatment holidays (Burstein et al, Proc ASCO 1999, abstr 484), suggesting no therapeutic advantage for uninterrupted therapy. The activity and tolerability of weekly docetaxel and Herceptin are encouraging and merit further investigation.