Hyperthermic intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil in patients at high risk of peritoneal metastasis from colorectal cancer: A preliminary clinical study.
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 confirmin vitrothe 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 at high risk of PM from CRC. To simulate HIPECin vitro, 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.
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Tomoharu
T
Shimizu
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Satoshi
S
Murata
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Hiromichi
H
Sonoda
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Eiji
E
Mekata
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Hiroyuki
H
Ohta
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Katsushi
K
Takebayashi
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Tohru
T
Miyake
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Tohru
T
Tani
5-fluorouracil; adjuvant; combination; hyperthermic intraperitoneal chemotherapy; mitomycin C