CT1 - Phase I Trial of Intraperitoneal Oxaliplatin in Combination with Intravenous FOLFIRI for Unresectable Peritoneal Carcinomatosis from Colorectal and Appendiceal Cancer

Background: The efficacy of bi-directional (IV and IP) chemotherapy in the management of peritoneal carcinomatosis (PC) from gynecologic malignancies has been demonstrated, but remains unknown in PC from GI malignancies.

Methods: Eligible patients with unresectable, isolated PC from colorectal or appendiceal cancer were enrolled in a Phase I, dose-escalation trial of 4 cycles of IP oxaliplatin in combination with IV FOLFIRI. Primary objective was to determine the MTD of IP oxaliplatin. Secondary objectives included: 1) determining the feasibility and safety of repeated IP oxaliplatin and 2) determine tumor response and PFS.

Results: Between October 2016 and October 2019, 12 patients have been enrolled. The mean age was 58 (range 34-71). 6 (50%) were male. 8 (67%) had appendiceal cancer. The MTD has not been reached at the highest dose cohort (80mg/m2). 3 (25%) did not complete the trial. Tumor response was identified in 9/12 (75%) patients and 5 (42%) patients underwent surgical exploration and/or cytoreduction. The most common side effects related to the intraperitoneal infusions were abdominal pain and distention, with some requiring IV pain medication. Elimination of the post-chemo 500 mL IP saline infusion with subsequent cycles negated the use for IV pain medication.

Conclusion: IP oxaliplatin can be safely delivered with concurrent IV FOLFIRI, with a MTD greater than 80mg/m2. A second, multi-institutional, Phase I trial with higher oxaliplatin doses is underway. Once the MTD is established, a phase II cooperative group study to determine the efficacy of this bi-directional chemotherapy treatment will be pursued.