Phase II multi-institutional prospective trial of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer refractory to fluoropyrimidine with modified dose reduction criteria (CCOG1303).

BACKGROUND The aim of this study was to explore the efficacy and safety of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer with modified dose reduction criteria by which the doses were manipulated earlier. METHODS Gastric cancer patients who developed progression during the fluoropyrimidine-containing first-line chemotherapy were assigned to receive nab-paclitaxel (260 mg/m2) by triweekly administration. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia less than 1000/mm3 and/or peripheral sensory neuropathy of grade 2 or more. The primary endpoint was progression-free survival. RESULTS A total of 50 patients were enrolled, 47 of whom were eligible for efficacy analyses. The median number of treatment cycles and relative dose intensity given per patient was four (range 1-25), and 90% (range 60-100). Of total administration throughout the trial of 280 cycles, dose reduction was required in 50 cycles. The median progression-free survival was 3.5 months (95% confidence interval 2.5-4.4) that met the primary endpoint. The median overall survival was 9.0 months (95% confidence interval 6.8-11.8), overall response rate was 16% (95% confidence interval 2-30), and disease control rate was 72% (95% confidence interval 54-90). The median time to treatment failure was 3.5 months (95% confidence interval 2.5-4.4). Adverse events of grade 3 or worse included neutropenia in 49%, and peripheral sensory neuropathy in 11%. Febrile neutropenia occurred only in one patient (2%). CONCLUSION The modified dose reduction criteria for triweekly administration of nab-paclitaxel resulted in decreased incidence of severe peripheral sensory neuropathy without decline in efficacy.