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

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.

• Authors: Shigeyuki Tamura, Hirokazu Taniguchi, Kazuhiro Nishikawa, Hiroshi Imamura, Junya Fujita, Atsushi Takeno, Jin Matsuyama, Yutaka Kimura, Junji Kawada, Motohiro Hirao, Masashi Hirota, Kazumasa Fujitani, Yukinori Kurokawa, Daisuke Sakai, Hisato Kawakami, Toshio Shimokawa, Taroh Satoh
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 25 Issue 12 Pg. 2035-2043 (Dec 2020) ISSN: 1437-7772 [Electronic] Japan
• PMID: 32926227 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

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

Topics

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