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

Int J Clin Oncol. 2020 Dec;25(12):2035-2043. doi: 10.1007/s10147-020-01768-w. Epub 2020 Sep 14.

Abstract

Background: For unresectable or recurrent advanced gastric adenocarcinoma (AGC), tri-weekly administration of nanoparticle albumin-bound paclitaxel (nab-PTX) at 260 mg/m2 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/m2) 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/m2) 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/m2) is not recommended for AGC in a second-line or later setting, despite demonstrating less toxicity than at 260 mg/m2. Clinical trial registration The OGSG1302 trial was registered with UMIN-CTR as UMIN000000714.

Keywords: Advanced gastric cancer; Nab-paclitaxel; Paclitaxel; Recurrent gastric cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Albumins / administration & dosage*
  • Albumins / adverse effects*
  • Albumins / therapeutic use
  • Anorexia / chemically induced
  • Anorexia / epidemiology
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Dose-Response Relationship, Drug
  • Fatigue / chemically induced
  • Fatigue / epidemiology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / epidemiology
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects*
  • Paclitaxel / therapeutic use
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / epidemiology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Treatment Outcome

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Paclitaxel