A phase II trial of dose-reduced nab-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-weekly nab-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 of nab-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-weekly nab-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.