Controversies Regarding the Optimal Dose of Nab-Paclitaxel Combined With Gemcitabine in a Phase 1 Trial of Patients with Metastatic Breast Cancer

Iwai M, Sato K, Fuchikami H, Mizuno Y, Matsumoto H, Ikehara Y, Mase T, Kawamoto S, Shimoyama R and Shinozaki N

Department of Pharmacy, Tokyo-West Tokushukai Hospital, Japan
Department of Breast Oncology, Tokyo-West Tokushukai Hospital, Japan
Department of Surgery, Hanyu General Hospital, Japan
Department of Surgery, Chubu Tokushukai Hospital, Japan
Department of Department of Breast and Endocrine Surgery, Ogaki Tokushukai Hospital, Japan
Department of Surgery, Fukuoka Tokushukai Hospital, Japan
Department of Surgery, Shonan Kamakura General Hospital, Japan
Department of Surgery, Shonan Fujisawa Tokushukai Hospital, Japan

^*Correspondance to: Kazuhiko Sato 

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Abstract:

Nano-particle albumin-bound paclitaxel (nab-paclitaxel) has shown significantly higher response rates and time to progression than has solvent-based paclitaxel in patients with metastatic breast cancer. The potential advantages of nab-paclitaxel led us to investigate the combination of nabpaclitaxel and gemcitabine instead of already proven combination regimens of paclitaxel with gemcitabine. Therefore, an open-label, multicenter, phase I trial was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of combination therapy with nabpaclitaxel and gemcitabine in patients with metastatic or recurrent breast cancer. Nab-paclitaxel was administered intravenously on day 1, and gemcitabine was administered intravenously on days 1 and 8 of a 21-day cycle. Nab-paclitaxel was administered at a starting dose of 220 mg/m2 (Level 1) and escalated to 260 mg/m2 (Levels 2-3), and gemcitabine was administered at a starting dose of 1,000 mg/m2 (Levels 1-2) and escalated to 1,250 mg/m2 (Level 3) by using a traditional 3 + 3 dose-escalation scheme in cohorts of three patients. Three patients were treated in Level 1 and no dose-limiting toxicities (DLT) occurred. In Level 2, additional patients were needed because one DLT was observed in 3 cohort patients. This study was ultimately terminated before defining the RD for two reasons: slow accrual and the results of a similar phase I study were reported by another study group. However, the result was different from ours. Although our study could not determine the MTD and RD, it illustrates that novel approaches should be considered to improve the efficiency of clinical studies.

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Cite the Article:

Iwai M, Sato K, Fuchikami H, Mizuno Y, Matsumoto H, Ikehara Y, et al. Controversies Regarding the Optimal Dose of Nab-Paclitaxel Combined With Gemcitabine in a Phase 1 Trial of Patients with Metastatic Breast Cancer. Clin Oncol. 2016; 1: 1070.