Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Higher Complication Rate for Oxaliplatin Compared to Mitomycin C

Abstract

Abstract.Background : Peritoneal carcinomatosis (PC) from colo-rectal cancer carries a very poor prognosis with a mean and median overall survival times of 6.9 and 5.2 months. It has been proved that a locoregional therapeutic approach of this disease with cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improved survival of these patients. However, this combined treatment presents a high complication rate. Methods : 21 patients with PC of colorectal origin underwent complete cytoreduction followed by HIPEC using Mitomycin-C (13 patients) or oxaliplatin (8 patients) and the open coliseum technique. For each case the medical datas were retrospectively analysed to determine feasibility, morbidity, mortality, survival time and prognostic factors. Results : All patients presented a Sugarbaker's Peritoneal Cancer index inferior to 15. The mean operating time was 453 minutes. After a median follow-up of 24.9 months, actuarial disease-free survival was 36.6% at 5 years. The median survival time was 34 months. The morbidity rate was 33.3% with a significant higher complication rate in the oxaliplatin group (5/8) than in the Mytomycin-C (MMC) group (2/13). One patient (4.7%) died two months after treatment with MMC (endocarditis). Conclusions : This series confirm positive impact of cytoreduction and HIPEC on PC. We obtained a moderated complications rate thanks to a high degree of selection of the patient. Oxaliplatin scheme is responsible of a higher morbidity than in MMC group. Phase III trial comparing these two drugs is needed.

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

“…Postoperative morbidity has to be taken into account when selecting an appropriate cytotoxic agent. Oxaliplatin has been suggested to cause higher morbidity rates with Grade II and III complication compared to MMC[ 27 ], as confirmed in this study. Reported complications in oxaliplatin trials include fistula formation, pneumonia or intraabdominal abscess formation[ 28 ].…”

Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: Results of the GYMSSA trial

“…Another difference to previous peritoneal surface management trials in mesothelioma and colorectal cancer is the choice of the regional chemotherapy agent - oxaliplatin compared to the previously more frequently used mitomycin C. Both agents have ample pharmacokinetic data available: when comparing maximum systemic exposure of both agents after HIPEC using standard 20mg/m2 mitomycin C or 400mg/m2 oxaliplatin, oxaliplatin reaches systemic peak PK levels, which are closer to its described maximum peak levels when given systemically when compared to mitomycin C.[40] That might, in addition to the differing mechanisms of action of the two agents, translate into increased bone marrow toxicity, and might cause more serious sequelae from septic complications as suggested by the findings of small retrospective series comparing the two HIPEC agents in the management of colorectal cancer peritoneal surface involvement. [41-43]…”

Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer

“…An additional treatment protocol each was described for the combination of MMC with 5-fluorouracil (5-FU) [125], the active irinotecan (IRI) metabolite hydroxycamptothecin (HCPT) [126] and etoposide (ETO) [119] (Table S7). Using single-agent oxaliplatin (L-OHP), at least twelve different manners of drug dosing were described in 44 articles published between 2002 and 2017 (Table S4) [28,31,32,33,34,35,54,55,60,65,66,69,72,75,76,81,82,91,108,111,116,121,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148]. Between 2004 and 2016 seven articles were published, outlining four diverse ways of dosing a combination of L-OHP and IRI (Table S5) [32,83,134,140,144,149,150].…”