Publication Year: 2000 Visited: 59

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Weekly Docetaxel (D) and Rhumabher2 (H) Combination Therapy as First- or Second-Line Treatment for Metastatic Breast Cancer (MBC). Brenda P. Nicholson, Ann D Thor, Lori J Goldstein, Douglas E Merkel, William J Gradishar, George W Sledge, Vanderbilt-Ingram Cancer Center/Vanderbilt-Ingram Cancer Ctr Affiliate Network, Nashville, TN; Evanston Hosp, Evanston, IL; Fox Chase Cancer Ctr, Philadelphia, PA; Northwestern Univ Medical Sch, Chicago, IL; Indiana Univ, Indianapolis, IN.

H and chemotherapy (CT) have been shown to improve time to progression, response rate and 1-yr survival compared with CT alone (Slamon, Proc Amer Soc Clin Onc.17:98a, 1998). H combined with D has synergistic activity, but has not been evaluated clinically. We are conducting a phase II pilot study to evaluate the safety and efficacy of weekly D (35 mg/m2 IV 6 of 8 weeks) combined with weekly H (2 mg/kg IV after an initial 4 mg/kg loading dose) as first- or second-line treatment in HER2 overexpressing (2+ or 3+) MBC. Pts with MBC who have received no more than 1 prior CT regimen for advanced disease, no prior taxane, and < 250 mg/m2 anthracycline are eligible. All tumors have been reviewed centrally using the DAKO method and overexpress HER2 (10 pts-HER2 3+; 4 pts-HER2 2+). Median age is 53 (range: 36-73). Median number of disease sites is 2 (range: 1-4). Four pts received no prior CT, 8 pts received prior adjuvant CT, and 2 pts received prior CT for metastatic disease. Preliminary toxicity data are available on 14 eligible pts and 26 cycles of therapy. One pt experienced G3 nausea, G4 neutropenia and neutropenic fever with cycle one. No other G3/4 toxicity was observed in any other pt. The most frequently reported non-hematologic toxicities were fatigue (3 pts-G2, 8 pts-G1), dyspepsia (2 pts-G2, 4 pts-G1), diarrhea (1 pt-G2, 5 pts-G1), and nausea (1 pt-G3, 2 pts-G2, 3 pts-G1). MUGA scans were performed at baseline and every 8 weeks. No pt experienced a symptomatic decline in ejection fraction (EF). An asymptomatic decline in EF from 68% at baseline to 52% was observed in 1 pt after 2 cycles. However, the EF returned to baseline (65%) without discontinuation of therapy or medical intervention. One CR and 6 PR's have been observed in 13 assessable patients (ORR 54%). The study will continue to accrue pts to a sample size of 34. Based on these preliminary data, the combination of weekly docetaxel and rhuMAb HER2 is well tolerated with significant anti-tumor activity. (Supported in part by grants from Genentech and Rhone-Poulenc Rorer)