Abstract
BackgroundIntraperitoneal (IP) administration of paclitaxel (PTX) has a great pharmacokinetic advantage to control peritoneal lesions and can be combined with various systemic chemotherapies. In this study, we evaluate the efficacy and tolerability of a combination of IP-PTX and systemic S-1/oxaliplatin (SOX) for induction chemotherapy for patients with peritoneal metastases (PM) from gastric cancer (GC).Patients and MethodsPatients with GC who were diagnosed as macroscopic PM (P1) or positive peritoneal cytology (CY1) by staging laparoscopy between 2016 and 2019 were enrolled. PTX was IP administered at 40 mg/m2 on days 1 and 8. Oxaliplatin was IV administered at 100 mg/m2 on day 1, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, repeated every 21 days. Survival time and toxicities were retrospectively explored.ResultsForty-four patients received SOX + IP-PTX with a median (range) of 16 (1–48) courses, although oxaliplatin was suspended due to the hematotoxicity or intolerable peripheral neuropathy in many patients. The 1-year overall survival (OS) rate was 79.5% (95% CI 64.4–88.8%) with median survival time of 25.8 months. Gastrectomy was performed in 20 (45%) patients who showed macroscopic shrinkage of PM with a 1-year OS rate of 100% (95% CI 69.5–100%). Grade 2 and 3 histological responses was achieved in four (20%) and one (5%) patients. Grade 3/4 toxicities included neutropenia (11%), leukopenia (39%), and anemia (14%). There were no treatment-related deaths.ConclusionsCombination chemotherapy using SOX + IP-PTX regimen is highly effective and recommended as induction chemotherapy for patients with PM from GC.
Highlights
Intraperitoneal (IP) administration of paclitaxel (PTX) has a great pharmacokinetic advantage to control peritoneal lesions and can be combined with various systemic chemotherapies
We developed a protocol combining weekly IP-PTX with S-1 and IV-PTX for patients with gastric cancer (GC) with peritoneal metastases (PM), which showed 1-year overall survival (OS) rates of 78% in patients with macroscopic (P1) or microscopic (P0CY1) PM21 and 77% in patients with P1 disease.[22]
Effects of S-1 and IV-PTX were less effective against the primary tumor as well as extraperitoneal metastases as compared with the activity against peritoneal lesions, which encouraged us to introduce other systemic regimens combined with IP-PTX
Summary
Intraperitoneal (IP) administration of paclitaxel (PTX) has a great pharmacokinetic advantage to control peritoneal lesions and can be combined with various systemic chemotherapies. Over the course of previous clinical studies, we performed conversion gastrectomy for patients who had disappearance or obvious shrinkage of PM after chemotherapy including IP-PTX, which showed excellent outcomes.[24,25] effects of S-1 and IV-PTX were less effective against the primary tumor as well as extraperitoneal metastases as compared with the activity against peritoneal lesions, which encouraged us to introduce other systemic regimens combined with IP-PTX.
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