Mustafa Raoof, M.D., M.S., Surgical Oncologist at the City of Hope. In this video, he speaks about the ASCO GI 2022 Abstract – Safety and efficacy of pressurized intraperitoneal aerosolized chemotherapy in appendiceal and colorectal cancer patients with peritoneal carcinomatosis: A first-in-US phase I study.
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Origins:
The use of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) as a potential minimally invasive palliative treatment for peritoneal metastases is being investigated (PM). Repeated PIPAC treatments in gastrointestinal and gynecologic cancers have been proven to be feasible and safe in previous investigations. The purpose of this phase 1 experiment was to determine the safety and feasibility of PIPAC oxaliplatin in patients with very chemotherapy-resistant colorectal and appendiceal cancer.
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Methodologies:
At two academic facilities, patients with biopsy-proven peritoneal metastases from colorectal or appendiceal cancer received up to three PIPAC treatments with oxaliplatin (92 mg/m2) at six-week intervals. Patients with intestinal obstruction, extraperitoneal metastases, or poor performance status (ECOG>2) were not included in the study. PIPAC was nebulized for 5 minutes with a 30 minute dwell time in the aerosol. The patients additionally got a sensitizing dosage of 5FU/LV (400mg/m2) within 24 hours of the operation, in addition to the initial PIPAC cycle. The primary end point was safety, which was determined by dose-limiting toxicities within six weeks of the first PIPAC. Safety, effectiveness, surgical morbidity, technical failure rate, progression-free and overall survival, pharmacokinetics (PK), and quality of life assessment were all secondary objectives.
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Findings:
A total of eight individuals were included in the study: five colorectal and three appendiceal. The median number of previous chemotherapy cycles was two (interquartile range: 1.5-3.5). Systemic oxaliplatin-based chemotherapy was ineffective in all of the patients. The median time between diagnosis and PIPAC was 16 months (IQR: 5.6–17.5), with a Peritoneal Carcinomatosis Index of 29. (IQR; 20.5, 31.5). Five patients (62.5%) completed three PIPAC cycles, while three patients (37.5%) had PIPAC stopped due to disease development in the peritoneal cavity. There were no surgical complications or dose-limiting toxicity. Only one patient acquired grade 3 treatment-related toxicity (anemia) after the first PIPAC, and another patient developed grade 3 treatment-related toxicity after the second PIPAC (abdominal pain and anemia). Five patients had stable disease at the end of PIPAC treatment, whereas three had disease progression. At the meeting, pharmacokinetic, histologic response, and preliminary survival data will be presented.
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Outcomes:
In a very chemotherapy-resistant cohort of appendiceal and colorectal carcinomatosis patients with or without sensitizing 5-FU/ LV, PIPAC with oxaliplatin is safe and feasible. NCT04329494 is the number for the clinical trial.