Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients with Locally Advanced Colon Cancer; the COLOPEC Randomized Trial

Abstract

Background: Patients with locally advanced (T4) or perforated colon cancer are at high risk (~25%) of developing peritoneal metastases (PM), often without curative treatment options. In this study, the effectiveness of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in reducing the development of PM was determined. Methods: In this multicentre non-blinded superiority trial, patients with c/pT4N0-2M0 or perforated colon cancer were randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy or to adjuvant systemic chemotherapy alone. Adjuvant HIPEC with oxaliplatin (460mg/m2, 30 minutes, 42°C, concurrent 5-FU/LV iv) was performed simultaneously (9%) or within 5-8 weeks (91%) after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was performed. The primary endpoint was PM free survival (PMFS) at 18 months. Findings: Between April 2015 and January 2017, 204 patients were randomized, 102 in each arm. In the control arm, 23 patients were diagnosed with PM, of which 7 by 18 months laparoscopy. In the experimental arm, 19 patients were diagnosed with PM, of which 9 during surgical exploration preceding intentional adjuvant HIPEC, 8 during routine follow-up and 2 by 18 months laparoscopy. In the intention to treat analysis (n=202), no difference in 18 months PMFS was observed; 76% (control) vs. 81% (experimental), HR 0·86 (0·51-1·45). After adjuvant HIPEC, 14% of patients developed postoperative complications and encapsulating peritoneal sclerosis occurred in one. PM were treated with cytoreductive surgery and HIPEC in 15/23 and 13/19 patients in the control and experimental arm, respectively. Interpretation: No superiority of adjuvant HIPEC with oxaliplatin could be demonstrated regarding 18 months PMFS in patients with T4 or perforated colon cancer. Trial registration number: NCT02231086 (Clinicaltrials.gov). Funding Statement: Organization for Health Research and Development (ZonMw) and the Dutch Cancer Society (KWF). Declaration of Interest: The authors have nothing to declare. Ethical Approval Statement: The Amsterdam UMC was the coordinating centre and approval of the protocol was obtained from its institutional review board.