A phase II trial of dose-reducednab-paclitaxel for patients with previously treated, advanced or recurrent gastric cancer (OGSG 1302)

Background For unresectable or recurrent advanced gastric adenocarcinoma (AGC), tri-weekly administration of nanoparticle albumin-bound paclitaxel (nab-PTX) at 260 mg/m(2)achieved a response rate of 27.8% in a phase II trial in Japan. However, frequent neutropenia and peripheral neuropathy limit its use in clinical settings. We, thus, conducted a single-arm phase II trial to investigate the efficacy and safety of a reduced dose (220 mg/m(2)) of tri-weeklynab-PTX. Methods Eligible patients included those with AGC and ECOG performance status of 0-2 who had received one or more prior chemotherapy containing fluoropyrimidine regimens. A reduced dose ofnab-PTX (220 mg/m(2)) was administered tri-weekly. The primary endpoint was response rate (RR). Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity (RDI) and proportion of patients receiving subsequent chemotherapy. Results Among 33 patients enrolled, 32 were treated with protocol therapy. RR was 3.1% [95% confidence interval (CI), 0-16.2%], which did not reach the protocol-specified threshold (p = 0.966). DCR was 37.5% (95% CI, 21.1-56.3%). Median OS and PFS were 6.3 (95% CI, 4.4-14.2) and 2.2 (95% CI, 1.8-3.1) months, respectively. RDI was 97.8%. Twenty (62.5%) patients received subsequent chemotherapy. Toxicity was relatively mild with the most common grade >= 3 adverse events being neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). Conclusion Tri-weeklynab-PTX with a reduced dose (220 mg/m(2)) is not recommended for AGC in a second-line or later setting, despite demonstrating less toxicity than at 260 mg/m(2). Clinical trial registration The OGSG1302 trial was registered with UMIN-CTR as UMIN000000714.