Mustafa Raoof1, Gautam Malhotra2, Adrian Kohut3, Michael O'Leary2, Paul Frankel4, Thuy Tran2, Marwan Fakih5, Joseph Chao5, Dean Lim5, Yanghee Woo2, Isaac B Paz2, Michael Lew6, Mihaela C Cristea5, Lorna Rodriguez-Rodriguez2, Yuman Fong2, Andrew Blakely7, Richard Whelan8, Marc A Reymond9, Amit Merchea10, Thanh H Dellinger11. 1. Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA. Mraoof@coh.org. 2. Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA. 3. Division of Gynecologic Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA, USA. 4. Biostatistics Core, City of Hope Beckman Research Institute, Duarte, CA, USA. 5. Department of Medical Oncology, COH, Duarte, CA, USA. 6. Department of Anesthesiology, COH, Duarte, CA, USA. 7. National Institute of Health, Bethesda, MD, USA. 8. Northwell Cancer Center, New York, NY, USA. 9. Tuebingen Universitaet, Tübingen, Germany. 10. Mayo Clinic, Jacksonville, FL, USA. 11. Division of Gynecologic Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA, USA. tdellinger@coh.org.
Abstract
BACKGROUND: Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS: This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS: Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS: The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.
BACKGROUND: Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS: This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS: Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS: The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.