PMID- 37501051 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240214 IS - 1534-4681 (Electronic) IS - 1068-9265 (Print) IS - 1068-9265 (Linking) VI - 30 IP - 12 DP - 2023 Nov TI - Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA. PG - 7814-7824 LID - 10.1245/s10434-023-13941-2 [doi] AB - BACKGROUND: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a laparoscopic locoregional treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery (CRS). While PIPAC has been studied in Europe and Asia, it has not been investigated in the USA. PATIENTS AND METHODS: We evaluated PIPAC with 90 mg/m(2) oxaliplatin alone (cycle 1) and preceded by systemic chemotherapy with fluorouracil (5-FU) and leucovorin (LV) (cycle 2-3) as a multicenter prospective phase I clinical trial (NCT04329494). The primary endpoint was treatment-related adverse events (AEs). Secondary endpoints included survival and laparoscopic, histologic, and radiographic response. RESULTS: 12 patients were included: 8 with CRC and 4 with AC. Median prior chemotherapy cycles was 2 (interquartile range (IQR) 2-3). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median peritoneal carcinomatosis index (PCI) was 28 (IQR 19-32). Six (50%) of twelve patients completed three PIPAC cycles. No surgical complications or dose-limiting toxicities were observed. Two patients developed grade 3 treatment-related toxicities (one abdominal pain and one anemia). Median overall survival (OS) was 12.0 months, and median progression-free survival (PFS) was 2.9 months. OS was correlated with stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but not with laparoscopic response by PCI or histologic response by peritoneal regression grading system (PRGS). CONCLUSIONS: This phase I trial in the USA demonstrated safety, feasibility, and early efficacy signal of PIPAC with oxaliplatin and chemotherapy in patients with PM from AC or CRC who are refractory to standard lines of systemic chemotherapy. CI - (c) 2023. The Author(s). FAU - Raoof, Mustafa AU - Raoof M AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. mraoof@coh.org. FAU - Whelan, Richard L AU - Whelan RL AD - Department of Surgery, Northwell Health, New York, NY, USA. rwhelan1@northwell.edu. FAU - Sullivan, Kevin M AU - Sullivan KM AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. FAU - Ruel, Christopher AU - Ruel C AD - Department of Computation and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA, USA. FAU - Frankel, Paul H AU - Frankel PH AD - Department of Computation and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA, USA. FAU - Cole, Sarah E AU - Cole SE AD - Department of Clinical Protocol Development, City of Hope National Medical Center, Duarte, CA, USA. FAU - Tinsley, Raechelle AU - Tinsley R AD - Clinical Trials Office, City of Hope National Medical Center, Duarte, CA, USA. FAU - Eng, Melissa AU - Eng M AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA. FAU - Fakih, Marwan AU - Fakih M AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA. FAU - Chao, Joseph AU - Chao J AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA. FAU - Lim, Dean AU - Lim D AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA. FAU - Woo, Yanghee AU - Woo Y AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. FAU - Paz, Isaac Benjamin AU - Paz IB AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. FAU - Lew, Michael AU - Lew M AD - Department of Anesthesiology, City of Hope National Medical Center, Duarte, CA, USA. FAU - Cristea, Michaela AU - Cristea M AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA. FAU - Rodriguez-Rodriguez, Lorna AU - Rodriguez-Rodriguez L AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. FAU - Fong, Yuman AU - Fong Y AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. FAU - Thomas, Rebecca Meera AU - Thomas RM AD - Department of Pathology, Norwell Health, New York, NY, USA. FAU - Chang, Sue AU - Chang S AD - Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA. FAU - Deperalta, Danielle AU - Deperalta D AD - Department of Surgery, Northwell Health, New York, NY, USA. FAU - Merchea, Amit AU - Merchea A AD - Department of Surgery, Mayo Clinic, Jacksonville, FL, USA. merchea.amit@mayo.edu. FAU - Dellinger, Thanh H AU - Dellinger TH AD - Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA. tdellinger@coh.org. LA - eng GR - P30 CA033572/CA/NCI NIH HHS/United States GR - P30 CA33572/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study DEP - 20230727 PL - United States TA - Ann Surg Oncol JT - Annals of surgical oncology JID - 9420840 RN - 04ZR38536J (Oxaliplatin) RN - 0 (Aerosols) RN - U3P01618RT (Fluorouracil) SB - IM MH - Humans MH - Oxaliplatin MH - *Appendiceal Neoplasms/drug therapy MH - *Peritoneal Neoplasms/secondary MH - Prospective Studies MH - Aerosols MH - Fluorouracil/therapeutic use MH - *Colorectal Neoplasms/drug therapy/pathology PMC - PMC10562297 EDAT- 2023/07/28 01:08 MHDA- 2024/02/10 14:49 PMCR- 2023/07/27 CRDT- 2023/07/27 23:37 PHST- 2023/04/28 00:00 [received] PHST- 2023/06/28 00:00 [accepted] PHST- 2024/02/10 14:49 [medline] PHST- 2023/07/28 01:08 [pubmed] PHST- 2023/07/27 23:37 [entrez] PHST- 2023/07/27 00:00 [pmc-release] AID - 10.1245/s10434-023-13941-2 [pii] AID - 13941 [pii] AID - 10.1245/s10434-023-13941-2 [doi] PST - ppublish SO - Ann Surg Oncol. 2023 Nov;30(12):7814-7824. doi: 10.1245/s10434-023-13941-2. Epub 2023 Jul 27.