Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer

Purpose: Efficacy and safety of nab-paclitaxel plus gemcitabine have not been clarified in Japanese patients with metastatic pancreatic cancer. No pharmacokinetic profile of co-administration of nab-paclitaxel and gemcitabine has been reported. We conducted a phase I/II study of the efficacy, safety, and pharmacokinetics in Japanese patients with metastatic pancreatic cancer. Methods: The patients were administered 125 mg/m² nab-paclitaxel followed by 1000 mg/m² gemcitabine on day 1, 8, and 15 every 4 weeks. Treatment was continued until disease progression, unacceptable adverse events, or withdrawal of consent, whichever occurred first. The primary endpoints were tolerability in phase I and overall response rate according to RECIST in phase II. Results: A total of 34 patients were enrolled. At the time of 1-year follow-up analysis since the last patient enrollment, the objective response rate by independent review committee was 58.8 % (20 of 34 patients; 95 % confidence interval [CI], 40.7-75.4 %). The median progression-free survival and median overall survival were 6.5 months (95 % CI, 5.1-8.3) and 13.5 months (95 % CI, 10.6 - not reached), respectively. Main adverse drug reactions of grade 3 or higher were neutropenia (70.6 %), leukopenia (55.9 %), anemia (14.7 %), lymphocytopenia (14.7 %), thrombocytopenia (14.7 %), and peripheral sensory neuropathy (11.8 %). There were no treatment-related deaths and no marked differences in pharmacokinetics of combined paclitaxel and gemcitabine in historical comparison between co-administration and monotherapies. Conclusions: Nab-paclitaxel plus gemcitabine regimen showed highly promising efficacy with manageable safety profile under careful observation and with appropriate supportive care in Japanese patients with metastatic pancreatic cancer. Clinical trial number: JapicCTI-121987.