Hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis surgery does not improve survival and may increase the rate of complications compared to surgery alone. This was the result of the French PRODIGE-7 study presented by François Quenet, Regional Cancer Institute, Montpellier, at the 2018 ASCO Annual Meeting in Chicago on June 5, 2018.
Peritoneal carcinomatosis is a metastatic tumor in the peritoneum that occurs in about 20% of patients with colorectal cancer. In many countries, hyperthermic intraperitoneal chemotherapy after surgical removal of the tumor is standard or at least an accepted therapy option. Without treatment, patients survive less than 6 months, with modern systemic chemotherapy about 16 months and with complete surgical removal plus HIPEC about 40 months, explained Quenet at an ASCO press conference. "When this approach was developed more than 15 years ago, we had the first effective treatment option for metastatic tumors in the abdomen, but we did not know whether or not the administration of heated chemotherapy during surgery was an important part of the treatment," he added. Quenet and his colleagues, therefore, investigated this question in a randomized study.
Between February 2008 and February 2014, 265 patients with stage IV colorectal cancer and peritoneal carcinomatosis were enrolled in the PRODIGE-7 study in France. 132 patients were operated on randomly, 133 patients underwent hyperthermal intraperitoneal chemotherapy (HIPEC) with oxaliplatin solution heated to 43 °C in addition to the operation. Most patients also received systemic chemotherapy at the doctor's discretion.
Mortality after 30 days was 1.5% in both groups, the side effect rate did not differ in the first 30 days in the two groups. However, after 60 days in the HIPEC group, the number of complications almost doubled compared to the non-HIPEC group (24.1% vs. 13.6%).
After a median follow-up period of 64 months, the median overall survival was 41.2 months in the non-HIPEC group and 41.7 months in the HIPEC group (HR 1.00 p = 0.995). Recurrence-free survival was also not significantly different (HR 0.908, p = 0.486) at 11.1 months in the non-HIPEC group and 13.1 months in the HIPEC group.
A subgroup analysis of the study indicates that HIPEC may benefit from HIPEC in patients with a mean peritoneal cancer index (PCI) - a measure of tumor mass - while it is unnecessary with a low index. With high PCI neither HIPEC nor operation have an effect. However, these figures are too small to draw conclusions.
"This study is very important and an example that less can be more. It proves that many patients can be spared unnecessary chemotherapy, often accompanied by severe side effects," said ASCO expert Andrew Epstein, Memorial Sloan Kettering Cancer Center, New York, at an ASCO press conference.
Quenet F, et al. A UNICANCER phase III trial of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis: PRODIGE 7. 2018 ASCO Annual Meeting, Chicago, June 1-5, 2018, abstract LBA4001. https://meetinglibrary.asco.org/record/158740/abstract