Publication Year: 2000 Visited: 85

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A Phase II Trial of Docetaxel and Herceptin in Metastatic Breast Cancer Patients Overexpressing HER-2. Michel E Kuzur, Kathy S Albain, Michael O Huntington, Suzanne F Jones, John D Hainsworth, Frank A Greco, Joan B Erland, Charles L Vogel, Howard A Burris, The Sarah Cannon Cancer Ctr andTennessee Oncology, Nashville, TN; Loyola Univ, Chicago, IL; Teton Medical Ctr, Idaho Falls, ID; Columbia Cancer Research Network of Florida, Aventura, FL.

The addition of Herceptin to chemotherapy in patients (pts) with Her-2 overexpressing breast cancers has been shown to improve not only response rate and time to tumor progression, but also survival. Docetaxel is highly active in the treatment of breast cancer, and has been shown in preclinical models to be synergistic with Herceptin. This phase II trial was designed to evaluate the efficacy as well as the safety profile of this combination in patients with measurable metastatic breast cancer. Herceptin is given on day 1 as a 4mg/kg loading dose, followed by 2mg/kg weekly until disease progression. Docetaxel 75mg/m2 q 3 weeks is administered on day 1 of each cycle after the Herceptin. Twenty-one pts have received 108+ cycles of docetaxel and 300+ doses of Herceptin (median age 54, range 36-72, 14 pts 3+ overexpression, 7 pts 2+ overexpression, 16 with prior chemotherapy). All patients' tumor specimens were sent to a central laboratory for determination of HER2 expression by the DAKO kit (immunohistochemistry). A median of 6 cycles per pt have been given and the median time on study is approximately 200 days. Toxicity has been minimal with 1 episode of febrile neutropenia, and 3 pts with ³grade 2 dermatitis. No clinically significant cardiotoxicity has been observed (no LVEF decline to £40%, no LVEF decline ³20%, and no symptoms). Of 16 pts evaluable for response (3 pts are too early to evaluate and 2 pts are inevaluable for response), 1 CR, 6 PRs, and 3 MRs have been observed. Six of the seven major responses were observed in 3+ overexpressing pts. Only 1 pt had progressive disease as her best response. Median time to progression currently exceeds 6 months. Three CNS relapses have been observed (including 2 as the only site), with patients continuing Herceptin post-whole brain irradiation. In summary, encouraging antitumor activity as demonstrated by both objective tumor responses and time to progression, as well as minimal toxicity, has been noted with this combination regimen.