GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

Residual tumour less than 0.25 centimetres and positive lymph nodes are risk factors for early relapse in recurrent ovarian peritoneal carcinomatosis treated with cytoreductive surgery, HIPEC and systemic chemotherapy.

AIM: The cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has showed promising results for the survival in patients with recurrent ovarian carcinomatosis, however, some of them will recur within the first year. The aim of this study is focussed on identifying the risk factors to develop the recurrence within the first year after an optimal CRS-HIPEC in patients with recurrent ovarian carcinomatosis. METHODS: A total of 100 patients with peritoneal carcinomatosis from recurrent ovarian cancer treated by CRS + HIPEC were selected for analysis. Multivariate logistic regression analysis was performed to evaluate the relationship between the variables and the early recurrence. RESULTS: The mean follow-up was 42.5 months. The mean age was 56.2 years. Early recurrence was observed in the 36%. The group early recurrence presented a higher rate of optimal cytoreductions CC1 (16.2% vs. 3.5%), lymph nodes (32.5% vs. 15%) and the use of hemoderivates (40.5% vs. 33%). Others parameters as Peritoneal Cancer Index, major morbidity? 3, re-operations rate and time to adjuvant chemotherapy were similar in both groups. The five years OS was 58%, for the non-early recurrence was higher than the early recurrence group (64% vs. 41%). In the multivariate analysis, CC-1 (OR 5.73; 1.16-32.04) and positive lymph nodes (OR 2.26; 1.01-4.32) proved to be independent factors for the early recurrence. CONCLUSION: The combination of both (CC1 and positive lymph nodes) makes that the indication of CRS and HIPEC should be individualised. However, the major morbidity, stage IV and the time to the adjuvant treatment were not associated with an early recurrence, so that, a major aggressiveness is recommended to achieve a CC0.