J Gastric Cancer.  2021 Dec;21(4):418-425. 10.5230/jgc.2021.21.e38.

Intraperitoneal Paclitaxel Combined with S-1 Plus Oxaliplatin for Advanced Gastric Cancer with Peritoneal Metastasis: a Phase I Study

• Kim DW
• Seo WJ
• Youn SI
• Jee YS
• Jang YJ
• Kim JH
• Perioperative Intra-Peritoneal & Systemic Chemotherapy for Gastric Cancer (PIPS-GC) study group

• KMID: 2526336
• DOI: http://doi.org/10.5230/jgc.2021.21.e38

Abstract

Purpose
We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients.
Materials and Methods
Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m² /day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m² , and the dose escalation was set in units of 20 mg/m² up to 80 mg/m² . Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia.
Results
Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m² . Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination.
Conclusions
The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m² , when combined with a systemic SOX regimen.

Keyword

Stomach neoplasm; Peritoneal neoplasm; Injections; Intraperitoneal; Clinical trial; phase I