PIPAC-MMC Plus FOLFIRI Shows Feasibility, Safety in Peritoneal Metastases

Of 19 patients treated with chemotherapy plus PIPAC-MMC across 3 dose levels, 1 (5.3%) attained a complete response, 2 (10.5%) attained a partial response, and 12 (63.2%) had stable disease per RECIST v1.1 criteria.

Mitomycin C pressurized intraperitoneal aerosolized chemotherapy (PIPAC-MMC) in combination with systemic chemotherapy showcased feasibility and tolerability as a treatment for a small cohort of patients with unresectable appendiceal and colorectal carcinomatosis, according to results from arm 3 of a phase 1 dose-escalation trial (NCT04329494) presented in a press briefing at the Society of Surgical Oncology (SSO) 2025 Annual Meeting.¹

Findings from the trial revealed that of 19 patients treated with chemotherapy plus PIPAC-MMC across 3 dose levels, 1 (5.3%) attained a complete response (CR), 2 (10.5%) attained a partial response (PR), and 12 (63.2%) had stable disease per RECIST v1.1 criteria. Of note, 1 patient (5.3%) experienced progressive disease, and an additional 3 (15.8%) were unassessed as of data cut-off.

Additionally, 15 (79%) patients exhibited histologic regression in this treatment group, with 6 (32%) attaining a complete pathologic response. A reduction in peritoneal cancer index (PCI) was observed in 84% of this patient group, with an average PIPAC1 to PIPAC3 reduction of 53%. Of note, 3 patients had single PIPAC at baseline.

Furthermore, carcinoembryonic antigen (CEA) decline was observed in 15 (79%) patients treated with PIPAC-MMC, with an average maximum reduction of 47.9%.

“PIPAC-MMC plus systemic leucovorin calcium [folinic acid], fluorouracil, and irinotecan hydrochloride [FOLFIRI] is feasible and safe,” Mustafa Raoof, MD, MS, chief of Mixed Tumor and Regional Therapies in the Department of Surgery of the Cancer Genetics and Epigenetics City of Hope Cancer Center, stated in the presentation.¹ “[Patients who received dose level 2 and 3] had better responses compare to [dose level] 1, but [patients who received dose level 3] had more severe adverse effects [AEs] and higher failure to complete protocol-specified treatment compared to those on [dose level 1 and 2].”

Patients with colorectal or appendiceal peritoneal metastases not eligible for resection were assigned to receive PIPAC-MMC across 4 levels, 3 of which were included in the analysis, and FOLFIRI. Patients were pretreated with cytotoxic therapy with or without a biologic treatment. Cytotoxic therapy consisted of either FOLFIRI; leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX); or oxaliplatin, irinotecan, leucovorin, 5-fluorouracil (FOLFOXIRI). Biologic therapies included anti-EGFR therapy for left-sided KRAS wild-type indications, and anti-VEGF therapy for others.

Patients received either 7 mg/m², 12.5 mg/m², 19 mg/m², or 25 mg/m² of PIPAC-MMC every 6 weeks for 3 cycles. FOLFIRI was given intravenously on weeks 2, 4, 8, 10, 14, and 16 of treatment. An optional laparoscopic biopsy was performed to evaluate patients for cytoreductive surgery.

Patients had a median age of 59.7 years (range, 31.1-79.0). A total of 11 (48.9%) were male, 16 (84%) were Caucasian, 15 (78%) had an ECOG performance status of 0, and 10 (52.6%) had appendiceal carcinomatosis. Eleven patients (57.9%) received 3 or more PIPAC cycles, and 4 (22.2%) were removed from treatment due to nebulizer supply issues. Of 15 patients who were treated and not impacted by nebulizer supply issues, 10 (66.7%) completed treatment, including 2 (100%) in the first dose level, 5 (100%) in the second dose level, and 3 (37.5%) in the third dose level.

The study’s primary end points included dose-limiting toxicities and AEs.² Secondary end points included responses, decreases in Peritoneal Regression Grading Score over successive biopsies, progression-free survival, and cytoreductive surgery rate.

The highest toxicity grade was 1 or 2 in 58% of patients treated on the trial and grade 3 or higher among 31% of patients. A total of 67%, 87%, and 25% of patients receiving dose levels 1, 2, and 3 experienced the highest toxicity grade of 1 or 2, and 0%, 12%, and 62%, respectively, experienced grade 3 or higher toxicities.

The most common grade 1 or 2 toxicities across dose levels included nausea (n = 7), anemia (n = 7), abdominal pain (n = 5), vomiting (n = 4), and abdominal distension (n = 4). The most common grade 3 toxicities were thrombocytopenia (n = 2) and abdominal pain (n = 2).

Reference

1. Raoof M. Dose escalation phase 1 trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for unresectable appendiceal and colorectal carcinomatosis. Presented at the Society of Surgical Oncology (SSO) 2025 Annual Meeting; March 27-29, 2025; Tampa, FL.
2. PIPAC for the treatment of peritoneal carcinomatosis in patients with ovarian, uterine, appendiceal, colorectal, or gastric cancer. ClinicalTrials.gov. Updated July 18, 2024. Accessed March 27, 2025. https://tinyurl.com/336ksybp