The addition of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery showed no overall survival (OS) benefit but was associated with more frequent postoperative late complications in patients with colorectal peritoneal metastases, according to the results of a study published in The Lancet Oncology.
Peritoneal metastases of colorectal origin are associated with reduced OS and significantly worse prognosis compared with nonperitoneal metastases. Although the clinical management of these patients has involved surgical resection in combination with HIPEC for more than a decade, there is a lack of prospective trials demonstrating the benefit of intraperitoneal chemohyperthermia in treating patients undergoing surgery for peritoneal carcinomatosis from colorectal cancer, the study authors stated.
In the open-label, phase 3 PRODIGE 7 trial (ClinicalTrials.gov Identifier: NCT00769405), researchers investigated the specific benefit of adding HIPEC to cytoreductive surgery compared with cytoreductive surgery alone. This prospective study was carried out at 17 cancer centers in France and included 265 patients with histologically proven colorectal cancer with peritoneal metastases of colorectal origin. The participants were randomly assigned 1:1 to cytoreductive surgery with (133 patients) or without oxaliplatin-based HIPEC (132 patients).
After a median follow-up of 63.8 months (interquartile range, 53.0-77.1), 59% of the patients in the cytoreductive surgery plus HIPEC group and 61% in the cytoreductive surgery group had died. The median OS in the cytoreductive surgery plus HIPEC group (41.7 months; 95% CI, 36.2-53.8) was not significantly different from the cytoreductive surgery group (41.2 months; 95% CI, 35.1-49.7) with a hazard ratio (HR) of 1.00 (95.37% CI, 0.63-1.58; stratified log-rank P =.99).
At 30 days, there were 2 treatment-related deaths in each group. Grade 3 or worse adverse events (AEs) included intra-abdominal, extra-abdominal, and hematologic complications that occurred at nearly similar frequencies at 30 days (P =.083). However, at 60 days, grade 3 or worse AEs occurred more frequently in the cytoreductive surgery plus HIPEC group than in the cytoreductive surgery group (26% vs 15%, respectively; P =.035).
Based on these results, the authors suggested that “High-dose oxaliplatin-based HIPEC given over a short duration should no longer be used, and macroscopically complete cytoreductive surgery should be considered the mainstay of treatment of peritoneal metastases.”
They further added, “Eligibility for surgical resection should be the main consideration in patients with colorectal cancer and peritoneal metastases. Such changes to clinical practice would spare patients with colorectal cancer from undergoing unnecessary intraperitoneal chemotherapy.”
Quénet F, Elias D, Roca L, et al; UNICANCER-GI and BIG Renape Group. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256-266. doi:10.1016/S1470-2045(20)30599-4