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 ... -  《-》

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 ... -  《-》

Long-term survival after hyperthermic intraperitoneal chemotherapy using mitomycin C or oxaliplatin in colorectal cancer patients with synchronous peritoneal metastases: A nationwide comparative study.

In the Netherlands, limited variability exists in performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among centers treating colorectal peritoneal metastases (PM), except for the intraperitoneal drug administration. This offers a unique opportunity to investigate any disparities in survival between the two most frequently used HIPEC regimens worldwide: mitomycin C (MMC) and oxaliplatin. This was a comparative, population-based cohort study of all Dutch patients diagnosed with synchronous colorectal PM who underwent CRS-HIPEC between 2014 and 2017. They were retrieved from the Netherlands Cancer Registry. Main outcome was overall survival (OS). The effect of the intraperitoneal drug on OS was investigated using multivariable Cox regression analysis. In total, 297 patients treated between 2014 and 2017 were included. Among them, 177 (59.6%) received MMC and 120 (40.4%) received oxaliplatin. Only primary tumor location was different between the two groups: more left-sided colon in the Oxaliplatin group (47.5% vs. 33.3%, respectively, p=0.048). The 1-, 2- and 3-year OS were 84.6% vs. 85.8%, 61.6% vs. 63.9% and 44.7% vs. 53.5% in patients treated with MMC and oxaliplatin, respectively. Median OS was 30.7 months in the MMC group vs. 46.6 months in the oxaliplatin group (p=0.181). In multivariable analysis, no influence of intraperitoneal drug on survival was observed (adjusted HR 0.77 [0.53-1.13]). Long-term survival between patients treated with either MMC or oxaliplatin during CRS-HIPEC was not significantly different.

Bakkers C ，van Erning FN ，Rovers KP ，Nienhuijs SW ，Burger JW ，Lemmens VE ，Aalbers AG ，Kok NF ，Boerma D ，Brandt AR ，Hemmer PH ，van Grevenstein WM ，de Reuver PR ，Tanis PJ ，Tuynman JB ，de Hingh IH ... -  《-》

Mitomycin-C versus oxaliplatin during cytoreductive surgery and HIPEC for peritoneal metastases secondary to colorectal carcinoma: a retrospective analysis.

Spiliotis J ，Kalles V ，Prodromidou A ，Raptis A ，Ferfelis M ，Christopoulou A ，Tsiatas M ... -  《-》

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, random

Rovers KP ，Bakkers C ，Simkens GAAM ，Burger JWA ，Nienhuijs SW ，Creemers GM ，Thijs AMJ ，Brandt-Kerkhof ARM ，Madsen EVE ，Ayez N ，de Boer NL ，van Meerten E ，Tuynman JB ，Kusters M ，Sluiter NR ，Verheul HMW ，van der Vliet HJ ，Wiezer MJ ，Boerma D ，Wassenaar ECE ，Los M ，Hunting CB ，Aalbers AGJ ，Kok NFM ，Kuhlmann KFD ，Boot H ，Chalabi M ，Kruijff S ，Been LB ，van Ginkel RJ ，de Groot DJA ，Fehrmann RSN ，de Wilt JHW ，Bremers AJA ，de Reuver PR ，Radema SA ，Herbschleb KH ，van Grevenstein WMU ，Witkamp AJ ，Koopman M ，Haj Mohammad N ，van Duyn EB ，Mastboom WJB ，Mekenkamp LJM ，Nederend J ，Lahaye MJ ，Snaebjornsson P ，Verhoef C ，van Laarhoven HWM ，Zwinderman AH ，Bouma JM ，Kranenburg O ，van 't Erve I ，Fijneman RJA ，Dijkgraaf MGW ，Hemmer PHJ ，Punt CJA ，Tanis PJ ，de Hingh IHJT ，Dutch Peritoneal Oncology Group (DPOG) ，Dutch Colorectal Cancer Group (DCCG) ... -  《BMC CANCER》