The PRODIGE 7 randomized, Phase III study, presented at ASCO 2018, has demonstrated that, for advanced colorectal cancer patients, hyperthermic intra-peritoneal chemotherapy (HIPEC) (heated chemotherapy) delivered to the abdomen during surgery, may not be necessary.
In patients with metastases in the abdomen receiving heated chemotherapy during surgery, no difference in survival were observed compared with patients receiving only surgery, and furthermore, side effects were seen to be more common with chemotherapy.
Peritoneal carcinomatosis occur in approximately 20% of metastatic colorectal cancer patients and in instances where the tumor can be completely removed, treatment consists of surgery with HIPEC. This treatment of surgery with HIPEC could prolong survival versus systemic therapy alone, and up to 16% of peritoneal carcinomatosis patients can be cured with surgery.
A total of 265 stage IV colorectal cancer patients with peritoneal carcinomatosis, were enrolled on the R&D UNICANCER-funded PRODIGE 7 trial. These patients had no metastases anywhere else in the body. The patients were randomly assigned to receive only surgery, or surgery with HIPEC. The HIPEC consisted of chemotherapy oxaliplatin heated to 43°C ,to try and improve the effectiveness of the chemotherapy. Ninety-six percent of the patients additionally received systemic therapy before surgery, after surgery, or both before and after surgery.
About HIPEC, lead study author Francois Quenet stated: “When this approach was introduced more than 15 years ago, it was the first effective treatment for metastatic tumors on a patient’s abdomen, but we didn’t know whether delivering heated chemotherapy during surgery was an important component of the treatment or not.”
With regards to PRODIGE 7, Quenet went on to explain, “This is the first randomized study assessing the role of this special type of chemotherapy in advanced colorectal cancer, and it shows that it does not provide added benefit over surgery.”
Delving further in to the main results, investigators demonstrated that at the median follow-up point of 64 months, the median overall survival for the non-HIPEC group was 41.2 months, and the median overall survival for the HIPEC group was 41.7 – a non-statistically significant difference. Recurrence-free survival was a median of 11.1 months in the non-HIPEC group and a median of 13.1 months in the HIPEC group.
No difference was observed in the rate of side effects during the first 30 days, although at 60 days, the rate of complications in the HIPEC group was 24.1% versus 13.6% in the non-HIPEC group. Overall mortality rate at 30 days after surgery was the same in both groups – 1.5%.
Further research is required to really investigate this deeper – ‘are there patients who would still benefit from receiving HIPEC with surgery?’ A subgroup analysis performed in the PRODIGE 7 study shows the possibility that HIPEC may be effective for patients with a ‘mid-range peritoneal cancer index’, howevr, the numbers analyzed were too small to be conclusive. Further studies can also look into whether other types of chemotherapy could be more beneficial than oxaliplatin, which used in PRODIGE 7.