Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC.

Colorectal peritoneal carcinomatosis (PC) is commonly treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is an ongoing international debate about which intraperitoneal chemotherapeutic agent is preferred, Mitomycin C (MMC) or oxaliplatin. We questioned whether the type of chemotherapeutic agent influenced postoperative complication rates or short-term survival. In this retrospective cohort study patients with colorectal PC who underwent CRS-HIPEC between January 2010 and December 2016 were included. Until March 2014 patients had preferentially been treated with MMC and thereafter with oxaliplatin in an iso-osmotic glucose/electrolyte dialysis (Dianeal®) carrier solution. Main outcomes were postoperative complications, disease free survival (DFS) and overall survival (OS). Survival analyses and multivariable analyses were performed. One hundred four patients received MMC and 73 patients oxaliplatin. Postoperative complications did not differ between groups (44.2% (MMC) versus 43.8% (oxaliplatin); P = 0.958). Median DFS was 12.5 months (IQR 6.4-32.4) in the MMC-group and 13.1 months (IQR 6.1-NA) in the oxaliplatin-group (P = 0.669). Median OS was 37.2 months (IQR 17.2-NA) in the MMC-group and 29.4 months (IQR 17.0-NA) in the oxaliplatin-group (P = 0.764). The type of chemotherapeutic agent did not influence OS in multivariable analysis (oxaliplatin versus MMC HR 1.09 (95%CI 0.58-2.06)). The HIPEC-phase was shorter for oxaliplatin (median 32 (IQR 31-34) versus 91 min (IQR 90-92) for MMC (P < 0.001)). Intraperitoneal oxaliplatin reduced the chemoperfusion time when compared to intraperitoneal MMC without adversely influencing complication rates or short-term survival. It may therefore be the preferential drug in CRS-HIPEC procedures for colorectal PC.

van Eden WJ ，Kok NFM ，Woensdregt K ，Huitema ADR ，Boot H ，Aalbers AGJ ... -  《-》

The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery. The American Society of Peritoneal Surface Malignancies (ASPSM) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C (MMC), stratifying them by the Peritoneal Surface Disease Severity Score (PSDSS). Median overall survival (OS) of 539 patients with complete cytoreduction was 32.6 months, 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group (P = 0.925). However, when stratified by PSDSS, median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin (P = 0.012), whereas in PSDSS III/IV patients, median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin (P = 0.427). These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC, favorable histologies and low burden of disease (PSDSS I/II) undergoing complete cytoreduction. Prospective studies are warranted, which stratify patients by their PSDSS and randomize them to HIPEC with MMC vs. Oxaliplatin.

Prada-Villaverde A ，Esquivel J ，Lowy AM ，Markman M ，Chua T ，Pelz J ，Baratti D ，Baumgartner JM ，Berri R ，Bretcha-Boix P ，Deraco M ，Flores-Ayala G ，Glehen O ，Gomez-Portilla A ，González-Moreno S ，Goodman M ，Halkia E ，Kusamura S ，Moller M ，Passot G ，Pocard M ，Salti G ，Sardi A ，Senthil M ，Spiliotis J ，Torres-Melero J ，Turaga K ，Trout R ... -  《-》

The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study.

Oxaliplatin and Mitomycin C (MMC) are both suitable as intraperitoneal chemotherapy agents in HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer (CRC). Patient cohorts from two different HIPEC-centers underwent cytoreductive surgery and HIPEC with Oxaliplatin (39 patients) and MMC (56 patients), respectively. They were compared for toxicity and survival data. The extent of PC was assessed using the Dutch 7-region count. The median 7-region count was 4 [range 0-7] for Oxaliplatin-patients versus 2.5 [range 1-6] for MMC-patients (P = 0.004). Median intra-operative blood loss was 650 ml [0-6,000 ml] in Oxaliplatin-patients versus 1,230 ml [range 0-5,300 ml] in MMC-patients (P < 0.001). Only MMC-patients developed neutropenia/leucopenia (26.8%, P < 0.001). After statistical correction for the extent of PC, the overall postoperative complication rate was significantly higher in MMC-patients (OR = 2.68 (95% CI: 1.04-6.91), P = 0.04), with a comparable intra-abdominal complication (IAC) rate (OR = 0.78 (95% CI: 0.30-2.03), P = 0.61), but a tendency towards more extra-abdominal complications (EAC) in MMC-patients (OR = 2.23 (95% CI: 0.91-5.43), P = 0.079). Median follow-up was significantly shorter for Oxaliplatin-patients (2.8 years) than for MMC-patients (5.1 years). Median RFS was 12.2 months [IQR: 7.2-undefined] in the Oxaliplatin-group and 13.8 months [IQR: 7.0-25.8] in the MMC-group (P = 0.87). Median OS is 37.1 months [IQR: 22.4-52.8] for Oxaliplatin-patients and 26.5 months [IQR: 16.9-64.8] for MMC-patients (P = 0.45). Logistic regression analysis (corrected for extent of PC) shows RFS (HR = 1.24 (95% CI: 0.75-2.05), P = 0.39) and OS (HR = 1.37 (95% CI: 0.74-2.54), P = 0.32) are not significantly different. No clear benefit in RFS and OS for HIPEC with Oxaliplatin or MMC could be demonstrated in patients with PC from CRC.

Hompes D ，D'Hoore A ，Wolthuis A ，Fieuws S ，Mirck B ，Bruin S ，Verwaal V ... -  《-》

Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis.

Compare long-term outcomes in colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC) treated with peritonectomy/HIPEC using oxaliplatin versus MMC. Peritonectomy and heated intraperitoneal chemotherapy (HIPEC) greatly improves patient survival in CRC PC. This procedure is not uniform across centres and the optimal choice of HIPEC chemotherapeutic is unclear. Oxaliplatin and Mitomycin C (MMC) are the most commonly used agents and comparative studies have reported varying results. 201 patients were retrospectively selected from the St George Hospital database, all of which had undergone peritonectomy/HIPEC for CRC PC. Oxaliplatin and MMC were used in 106 and 96 patients, respectively. Each patient's baseline characteristics, operative details, choice of chemotherapeutic agent and survival were noted. The two groups did not differ significantly at baseline. Patients receiving oxaliplatin had significantly greater unadjusted median survival compared to MMC (56.0 ± 8.1 vs. 29.0 ± 3.4 months) which translated into a hazards ratio of 0.59 (95% CI 0.37-0.91, p = 0.017). Subgroup analysis further confirmed an advantage with oxaliplatin in females, moderate-well differentiated tumours, tumours without signet ring pathology and PCI 10-15. Our study suggests oxaliplatin offers a survival advantage over MMC when used for HIPEC in CRC PC. Further studies to understand its efficacy, complications and ideal preparation are required. A Phase III randomised control trial comparing oxaliplatin and MMC would enhance decision-making.

Leung V ，Huo YR ，Liauw W ，Morris DL ... -  《-》

Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer.

The role of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin in addition to cytoreductive surgery (CRS) has recently been questioned in peritoneal metastases of colorectal cancer. Whether this applies to all published CRS/HIPEC regimens is unclear. A systematic literature search identified 46 studies on CRS/HIPEC using either oxaliplatin of mitomycin C with at least one oncological outcome parameter RESULTS: Oxaliplatin and mitomycin C studies were comparable regarding extent of disease, but differed substantially regarding synchronous versus metachronous presentation, application of neo-adjuvant systemic chemotherapy, duration of HIPEC, and completeness of cytoreduction for at least one of the oncological endpoints. Severe postoperative complication rate seemed significantly higher after oxaliplatin-based CRS/HIPEC. Published cohorts on oxaliplatin-based CRS/HIPEC differed essentially from MMC-based procedures, especially considering the application of oxaliplatin-containing neo-adjuvant systemic therapy and shorter exposure time to intraperitoneal chemotherapy in oxaliplatin studies. No meaningful comparison could be made regarding DFS and OS.

Wisselink DD ，Braakhuis LLF ，Gallo G ，van Grevenstein WMU ，van Dieren S ，Kok NFM ，de Reuver PR ，Tanis PJ ，de Hingh IHJT ... -  《-》