The role of oxaliplatin-based HIPEC in the treatment of peritoneal carcinomatosis from colorectal origin: friend or foe?

Several studies have shown improved survival outcomes in selected patients with peritoneal carcinomatosis of colorectal origin treated with cytoreductive surgery and HIPEC, as opposed to a treatment based on systemic chemotherapy alone. However, the most recent studies concerning oxaliplatin-based HIPEC have shown unexpected outcomes. Waiting for the paper to be published, the results of the Prodige 7 trial were released during the 2018 American Society of Clinical Oncology Meeting. In this phase 3 multicenter study, two hundred sixty-five patients were randomized to either cytoreductive surgery + HIPEC with 30-min oxaliplatin or cytoreductive surgery alone, in association with systemic chemotherapy. The outcomes showed that cytoreductive surgery alone showed unexpected satisfactory survival outcomes, with no differences in the overall survival neither the relapse-free survival between cytoreductive surgery + HIPEC or cytoreductive surgery alone. Besides, the 60-day morbidity was higher in the HIPEC group. 

The Prophylochip trial is another multicenter randomized phase 3 trial, which was designed with the goal of assessing the potential survival benefit of a systematic second-look surgery + HIPEC with oxaliplatin in patients at high risk of developing peritoneal carcinomatosis. The inclusion criteria of this study were patients with colorectal cancer presenting any of the following features at the time of primary resection: minimal resected carcinomatosis, ovarian metastases, or perforation of the primary tumor or iatrogenic rupture during surgery. These patients were treated with 6 months of adjuvant chemotherapy, and in case of no evidence of recurrence at the end of it, they were randomized to surveillance (the control arm) or second-look surgery + HIPEC (the experimental arm). No differences were found in 3-years disease-free survival neither overall survival.

Very recently, the outcomes of the COLOPEC trial were published in Lancet. Again, this is a study which analyzed the effect of adjuvant prophylactic HIPEC in patients with colonic tumors at high risk of developing peritoneal carcinomatosis. In this case, only patients with primary perforated or T4 tumors were included. This was a randomized trial which included 102 patients in the control arm (this means systemic chemotherapy alone) and 102 patients in the experimental arm (adjuvant HIPEC). The primary endpoint was peritoneal metastases-free survival at 18 months, for which an exploratory laparoscopy was carried out. Again, no differences were found between both arms, reinforcing the fact that routine adjuvant HIPEC is not advocated in these patents.

Does this mean that HIPEC should be abandoned?

No. This means that HIPEC with high dose of oxaliplatin and for 30 minutes should be questioned. In this video we will discuss these studies and the current role of oxaliplatin for 30 min.