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Biweekly Paclitaxel and Gemcitabine in Advanced Breast Cancer. Phase II Trial and Predictive Value of HER2 Extracellular Domain (ECD). Ramon Colomer, Antonio Llombart, Ana Lluch, Belen Ojeda, Agusti Barnadas, Vicente Caranana, Yolanda Fernandez, Laura De Paz, Vicente Guillem, Sagrario Montero, Silvia Alonso, Hosp 12 de Octubre, Madrid, Spain; Inst Valenciano de Oncologia, Valencia, Spain; Hosp Clin, Valencia, Spain; Hosp Sant Pau, Barcelona, Spain; Hosp Germans Trias i Pujol, Barcelona, Spain; Hosp Arnau de Vilanova, Valencia, Spain; Hosp Gen Yague, Burgos, Spain.

Patients and methods: Forty-three chemonaive patients with metastatic breast carcinoma were enrolled, and received paclitaxel 150 mg/m2 followed by gemcitabine 2500 mg/m2, both on day 1 of 14-day cycles. HER2 ECD was determined prospectively using an ELISA. All patients were evaluable for toxicity, and 42 were evaluable for efficacy. Results: Median age was 53 years, median PS was 100 (70-100), median number of lesions was 3, ER status was positive in 64%. Most patients (72%) had prior adjuvant therapy. Elevated HER2 ECD (>450 fmol/ml) was observed in 15/42 cases (36%). Grade 4 toxicity was limited to leukocytes and neutrophils (8% and 17%, respectively). Grade 3 toxicities consisted of AST elevation (8%), and thrombocytopenia, nausea and vomiting, neurosensory and constipation (4% each). One patient had neutropenia and fever. Objective response rate was 69% (24% CR; 45% PR); 19% had SD; 12% had PD. With a median follow-up of 11.5 months, median duration of response was 9 months (95% CI: 5-13 months). Response rate correlated significantly with HER2 ECD levels as seen in the table (p=0.003). Response duration was shorter in patients with positive HER2 ECD levels (6 vs 10.5 months, p=0.06) Conclusion: Paclitaxel plus gemcitabine given as a 2-week schedule to patients with untreated advanced breast carcinoma is an active regimen with a favorable toxicity profile. In addition, elevated levels of HER2 ECD affect adversely the response rate and the duration of response, which confirms the results of our previous trial.