Phase 2 randomized controlled trial of intravenous or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 as first-line treatment of advanced gastric cancer

Shen Zhao; Liyu Su; Yigui Chen; Xiaofeng Li; Peicheng Lin; Wujin Chen; Wenzheng Fang; Jinfeng Zhu; Hui Li; Liping Ren; Jie Liu; Yanni Hong; Shaowei Lin; Nanfeng Fan; Rongbo Lin

doi:10.3389/fonc.2022.850242

Phase 2 randomized controlled trial of intravenous or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 as first-line treatment of advanced gastric cancer

Front Oncol. 2022 Sep 7:12:850242. doi: 10.3389/fonc.2022.850242. eCollection 2022.

Authors

Shen Zhao^{1

2}, Liyu Su¹, Yigui Chen¹, Xiaofeng Li³, Peicheng Lin⁴, Wujin Chen⁵, Wenzheng Fang⁶, Jinfeng Zhu³, Hui Li¹, Liping Ren⁵, Jie Liu¹, Yanni Hong³, Shaowei Lin⁷, Nanfeng Fan¹, Rongbo Lin^{1

2}

Affiliations

¹ Department of Gastrointestinal Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
² Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
³ Department of Medical Oncology, Quanzhou First Hospital, Quanzhou, China.
⁴ Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
⁵ Department of Medical Oncology, Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.
⁶ Department of Medical Oncology, The 900th Hospital of Joint Logistic Support Force People's Liberation Army, Fuzhou, China.
⁷ School of Public Health, Fujian Medical University, Fuzhou, China.

Abstract

Objective: We conducted a phase 2 trial to compare the safety and efficacy of intravenous paclitaxel or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 in untreated advanced gastric cancer.

Methods: Participants with untreated advanced gastric cancer were randomly assigned (1:1:1) to: intravenous paclitaxel 135 mg/m² or intraperitoneal paclitaxel 80 mg/m² plus mFOLFOX6 omitting bolus fluorouracil; or mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² bolus, fluorouracil 2,400 mg/m² 46-h continuous infusion). Treatment was every 14 days for up to 9 cycles followed by S-1 maintenance. The primary outcome was progression-free survival.

Results: Of 90 enrolled participants, 30 in the intravenous paclitaxel group, 29 in the intraperitoneal paclitaxel group, and 30 in the mFOLFOX6 group were included in the analyses. The median progression-free survival was 6.52, 5.83, and 4.55 months, respectively, for the intravenous paclitaxel group, intraperitoneal paclitaxel group, and mFOLFOX6 group. The hazard ratios were 0.56 (95% CI: 0.33-0.94; p = 0.026) and 0.56 (95% CI: 0.33-0.96; p = 0.037), respectively, for the intravenous paclitaxel group and the intraperitoneal paclitaxel group vs. the mFOLFOX6 group. The most common grade 3/4 adverse events for the intravenous paclitaxel group, intraperitoneal paclitaxel group, and mFOLFOX6 group, respectively, were neutropenia (30.0%, 34.5%, 33.3%), diarrhea (13.3%, 20.7%, 13.3%), and leukopenia (10.0%, 13.8%, 10.0%). No treatment-related death occurred.

Conclusion: The findings of this phase 2 trial suggest that adding intravenous paclitaxel or intraperitoneal paclitaxel to mFOLFOX6 for untreated advanced gastric cancer improved progression-free survival with manageable adverse events.

Keywords: advanced; gastric cancer; intraperitoneal; intravenous; paclitaxel.