Hyperthermic intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil in patients at high risk of peritoneal metastasis from colorectal cancer: A preliminary clinical study

Abstract

Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been extensively used to treat patients with peritoneal metastases (PM) from colorectal cancer (CRC), a standard protocol has not yet been established. The aim of this preliminary clinical study was to confirm the efficacy of mitomycin C combined with 5-fluorouracil (MMC-5FU) under hyperthermic conditions in CRC and investigate the pharmacokinetics and feasibility of HIPEC with MMC-5FU for patients athigh risk of PM from CRC. To simulate HIPEC , we used the collagen gel droplet-embedded culture drug sensitivity test with the HCT166 colorectal cell line to assess the antitumor efficacy of MMC and 5FU as single-agent and combination treatments following incubation with HCT116 cells for 30 min at either 37 or 42°C. In addition, five patients at high risk of PM from CRC underwent surgical tumor resection followed by HIPEC with MMC-5FU. Our results demonstrated that the combined administration of MMC-5FU suppressed tumor cell proliferation more efficiently compared to either agent used alone. In addition, hyperthermia at 42°C significantly enhanced drug sensitivity. During the clinical application of HIPEC with MMC-5FU, no grade 4 hematological toxicities or surgical adverse events were recorded. In addition, there was no evidence of peritoneal recurrence during a median observational period of 38 months. Of note, two patients with positive intraoperative peritoneal cytology at the first surgery developed no peritoneal recurrence and exhibited negative peritoneal cytology at the second surgery. In conclusion, HIPEC using MMC-5FU was shown to be a feasible therapeutic option, with an acceptable toxicity profile, for patients at high risk of PM from CRC. Therefore, HIPEC with MMC-5FU may be a promising novel therapeutic option for such patients, which merits further verification of its safety and efficacy in large-scale clinical trials.

The Temperature-Dependent Effectiveness of Platinum-Based Drugs Mitomycin-C and 5-FU during Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer Cell Lines

“…Murata et al demonstrated that 5-FU was concentration-dependent in gastric cancer cells, and combined with cisplatin or MMC, the tumor cell growth effect was significantly inhibited compared with monotherapy [53]. Additionally, in CRC cells, the administration of MMC and 5-FU resulted in suppressed tumor cell proliferation compared with either agent used alone [54]. 5-FU alone or in combination with MMC can be a promising drug for the application of HIPEC for PMCRC patients.…”

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

“…In MMC/doxorubicin (DOX) combinations, we noticed three different reports considering drug dosage among merely four publications (Figure 2a, Table S3) [121,122,123,124]. 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].…”

“…Various cytostatic drugs were infrequently used, including CDDP monotherapy [108,147] (Table S6) and a number of other drugs limited to one or two publications only (5-FU/IRI/L-PAM; Table S8) [139,151,152,153]. Considering rare drug combinations, HIPEC conduct with mixtures of MMC and ETO, 5-FU as well as HCPT were reported (Table S7) [119,125,126]. A triple drug combination was an exemption [127].…”

The Effect of the Nano-Drug Carbomicin Inhibiting the Relapse of Stomach Cancer after Radiofrequency Ablation

“…The RFA technology has recently been successfully used for the treatment of liver cancer, lung cancer, pancreatic cancer, as well as other solid tumors in adrenal glands, kidneys, and breasts [6]. However, RFA also has some limitations as a tumor therapy [37]. Due to its irregular and invasive features, the tumor growth will lead to incomplete tumor ablation and, because any residual tumor tissue can rapidly grow when in a nutrient-rich environment (blood supply), tumor relapses are often experienced.…”

“…To improve the RFA treatment and prevent residual tumors from growing, this study used the mesoporous ACNP to adsorb MMC and developed a nano drug delivery system (NDDS) where ACNP acts as the carrier of the MMC drug. ACNP was chosen because of its; longevity in target tissues [36]; large drug loading capacity, due to their graphene composition [39] and the tortuous nanopores deepening into the core of the particles; wide adsorption spectrum and great inner absorption area [37]; and nontoxicity [40]. MMC is a proven effective anticancer drug [35] capable of almost completely killing the human stomach cancer BGC-823 cells.…”