Dr Aranha on Data Informing HIPEC Use in Peritoneal Carcinomatosis of GI Malignancies

Olivia Aranha, MD, PhD, associate professor, John T. Milliken Department of Medicine, Division of Oncology, Washington University School of Medicine discusses data supporting the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal carcinomatosis in gastrointestinal malignancies, as well as which populations should or should not receive this approach.

Aranha begins by stating that caution should be exercised when considering HIPEC for patients with a high disease burden. If systemic therapy has not effectively controlled their disease or if they have a peritoneal cancer index (PCI) score exceeding 25, the impact of HIPEC may be limited, she adds.

The potential benefits of cytoreduction with HIPEC was originally demonstrated in a landmark trial conducted in the Netherlands in 2003, Aranha reports. The study enrolled 105 patients with peritoneal carcinomatosis of colorectal cancer who were randomly assigned to receive either standard systemic chemotherapy with or without palliative surgery, or aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regimen. The primary end point was survival. The median survival for patients undergoing cytoreduction with HIPEC in this trial was significantly longer vs those receiving standard therapy, Aranha states. At a median follow-up of around 21.6 months, the median survival was 22.3 months vs 12.6 in the control vs HIPEC arms, respectively. This survival benefit was particularly noted among patients who achieved an R1 resection, she notes.

Another key trial informing the use of HIPEC was the phase 3 PRODIGE-7 study (NCT00769405), evaluating cytoreductive surgery (CRS) alone versus CRS combined with oxaliplatin-based HIPEC, Aranha continues. The study included patients with a PCI score less than 25, she says. All patients received 12 cycles of perioperative systemic chemotherapy consisting of multidrug chemotherapy combinations, including FOLFOX (5-FU, leucovorin, and oxaliplatin) or FOLFIRI (5-FU, leucovorin, and irinotecan). Patients were then randomized to cytoreduction with or without HIPEC. In the CRS-HIPEC arm, HIPEC was delivered with 460 mg/m2 of oxaliplatin for 30 minutes. One hour before the HIPEC, 20 mg/m2 of leucovorin and 400 mg/m2 of 5-FU given intravenously 1 hour before the HIPEC.

Although the study did not show an overall survival advantage for the addition of HIPEC, a post-hoc subgroup analysis revealed promising results for patients with a lower PCI score of 11 to 15, Aranha states. In this subgroup, those who underwent CRS-HIPEC demonstrated longer median overall survival (OS) and relapse-free survival compared with those who underwent cytoreductive surgery alone, with median OS substantially exceeding expectations, she reports. These findings underscore the importance of carefully selecting patients for HIPEC based on disease burden and PCI score, Aranhaconcludes.