3: Bidirectional paclitaxel-based chemotherapy for gastric adenocarcinoma with isolated peritoneal metastasis

Gastric cancer is the fourth leading cause of cancer deaths worldwide. Approximately 15-30% of affected individuals present with peritoneal metastases at the time of diagnosis and up to 70% will develop peritoneal carcinomatosis during the disease course. The efficacy of locoregional therapy with intraperitoneal (IP) drug delivery for gastric peritoneal carcinomatosis is understudied. The aim of our study was to determine intraperitoneal progression-free survival (PFS) and overall survival (OS) in patients with peritoneal metastases from gastric adenocarcinoma who received intravenous and intraperitoneal paclitaxel plus oral capecitabine.


Methods:

We conducted an open label, single-institution phase II study in patients with stage IV gastric adenocarcinoma with peritoneal-only metastasis (ClinicalTrials.gov NCT04034251). Twelve patients were enrolled and received IP paclitaxel low-dose 20 mg/m² (n=5) or high-dose 60 mg/m² (n=7) plus intravenous paclitaxel 80 mg/m² every 3 weeks and oral capecitabine 825 mg/m² twice daily for the first 14 of each 21 days. The goal for total duration of therapy was 9 weeks. The primary endpoint was intraperitoneal PFS and secondary endpoints included OS, frequency of serious and non-serious adverse events, and extra-peritoneal disease progression.


Results:

Twelve patients with a median age of 50 years were enrolled from 1/21/2020 to 8/25/2022. One participant had rapid progression of disease prior to IV/IP Taxol treatment initiation and was excluded from our analysis. All patients received systemic chemotherapy prior to enrollment. For individuals receiving low-dose IP paclitaxel, median PFS was 4.2 months (95% CI 1.5–NA) and OS was 10.6 months (95% CI 4.7–12.5). One patient in this group developed extra-peritoneal disease progression during the study period. The study was amended to increase the IP Taxol dose to 60 mg/m², and in this group median PFS was 13.3 months (95% CI 1.5–13.3) and OS was 14.7 months (95% CI 4.0–17.7). All patients (100%, 11/11) sustained at least one non-serious adverse event and one patient (9%, 1/11) sustained a serious adverse event during the study period.


Conclusions:

Bidirectional paclitaxel-based chemotherapy is safe and may delay progression of gastric adenocarcinoma with peritoneal-only metastasis. Higher doses of IP paclitaxel are well-tolerated and may be associated with improved responses to therapy. Additional clinical trials are needed to investigate bidirectional therapy for gastric carcinomatosis.