Phase 1 trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and carcinomatosis or positive cytology.

[BACKGROUND] The purpose of this phase 1 trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel (PTX) for patients with gastric cancer metastatic to the peritoneum.

[METHODS] A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel at weekly treatments for 3 weeks, followed by a 1-week break, and then three additional treatments. The primary objective was to define the maximum tolerated dose. Secondary end points included safety, tolerability, and antitumor activity.

[RESULTS] A total of 25 patients were treated between January 2020 and April 2023. Five dose-limiting toxicities were observed at 100 mg/m. Treatment-related grade 3-4 toxicity included leukopenia (32%) and neutropenia (32%). Seven patients required a schedule change to every other week treatments. The maximum tolerated dose for intraperitoneal PTX was 100 mg/m. The peritoneum post-intraperitoneal PTX demonstrated progression in five (20%), stable disease in five (20%), improvement in 10 (40%), and not evaluable in five (20%). Eight patients (32%) had resolution of their peritoneal disease and seven (28%) underwent attempted resection. The median overall survival (OS) from the diagnosis of metastatic disease was 18.8 months and from the date of treatment initiation was 10.8 months. One-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 84%, 38%, and 25%, respectively.

[CONCLUSIONS] Paclitaxel may be safely used at intraperitoneal doses of 100 mg/m. Neutropenia associated with weekly treatments was common. Peritoneal complete clinical response rates with multimodality therapy including PTX were promising.