Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer

Abstract

BACKGROUND Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited. AIM To evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors. METHODS One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient’s demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival. RESULTS The two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis. CONCLUSION In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.

Peritoneal Metastasis: A Dilemma and Challenge in the Treatment of Metastatic Colorectal Cancer

“…A study by Charrier et al showed that HIPEC-OXL increased the risk of postoperative bleeding compared with other agents (15.7% vs. 2.6%; p = 0.004) [183]. Similar results were found in a retrospective study, in which there was no difference in mOS between the two groups using MMC or OXL, patients treated with HIPEC-OXL had increased complication rates compared to those receiving MMC (66.2% vs. 35.3%; p = 0.003), especially bowel weakness, intra-abdominal infections, and urinary tract infections [184]. In contradiction, in the study by Delhorme et al, the DFS and peritoneal DFS (PDFS) were significantly better in the MMC group than the OXL group, and there was no difference in the OS and complication rates between the two groups [185].…”

2022 Peritoneal Surface Oncology Group International Consensus on HIPEC Regimens for Peritoneal Malignancies: Colorectal Cancer

“…Dosage varied considerably for MMC (12.5-40 mg/ m 2 ) and OX (200-460 mg/m 2 ), which was combined with irinotecan in one of the studies. [24][25][26][27][28][29][30][31][32][33][34] Recently, Zhang et al performed a systematic review and meta-analysis of comparative studies regarding these two HIPEC regimens and concluded there was no survival benefit for either regimen over the other. Significantly more complications occurred in patients receiving OX-based HIPEC.…”

Current Trends in Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Disease from Appendiceal and Colorectal Malignancies

“…Additional retrospective analyses have shown mixed results when evaluating the efficacy and safety profiles between these commonly used agents when treating CRC, but more studies demonstrate equivalent efficacy [ 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 ]. Further studies comparing oxaliplatin vs. MMC + doxorubicin [ 197 ], irinotecan vs. oxaliplatin [ 198 ], oxaliplatin ± irinotecan [ 181 , 199 ], and MMC vs. melphalan [ 200 ] have been performed but have not yielded a definitively superior regimen.…”