In vitro thermochemotherapy of colon cancer cell lines with irinotecan alone and combined with mitomycin C.
OBJECTIVE
Irinotecan (CPT-11) is a new drug of the camptothecin family which has shown significant activity in the treatment of metastatic colorectal cancer. Hyperthermia has been shown to enhance the cytotoxic effect of some anticancer drugs and has been combined with intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis. The purpose of this study was to evaluate the cytotoxic effect of CPT-11 alone and in combination with mitomycin C (MMC) and hyperthermia on three colorectal cancer cell lines: CACO-2, HT-29, and DHD/K12/TRb (PROb).


METHODS
The cytotoxic effect of CPT-11 was tested at seven different concentrations (from 2.5 to 160microg/mL) for each type of cell line at 37, 39, 42.5 and 44 degrees C. Combined cytotoxic effect of MMC with CPT-11 was tested at 37 and 42.5 degrees C.


RESULTS
The cytotoxic effect of CPT-11 alone increased with concentration (p<0.001) and with increasing temperature (p<0.001) at concentration above 5microg/mL in all three cell lines. CPT-11 (20microg/mL) significantly increased the cytotoxicity of MMC (8microg/mL) at 42.5 degrees C on the CACO-2 line. The combination of CPT-11 and MMC had at least 92% cytotoxicity on the three cell lines.


CONCLUSIONS
The combination of CPT-11 and MMC at 42.5 degrees C had a large spectrum of cytotoxicity in these in vitro models. Our findings support the clinical use of this combination and provide a rationale for the design of a clinical trial using intraperitoneal chemohyperthermia with MMC and CPT-11 to treat colorectal peritoneal carcinomatosis of colorectal origin.
Le Page
Sébastien
S
Oncologic Hyperthermia Laboratory-EA 3738, Université C B Lyon-1, Oullins, France.
Kwiatkowski
Fabrice
F
Paulin
Christian
C
Mohamed
Faheez
F
Pezet
Denis
D
Chipponi
Jacques
J
Benhamed
Mohamed
M
Gilly
François Noël
FN
Glehen
Olivier
O
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D006801:Humans; D006979:Hyperthermia, Induced; D000077146:Irinotecan; D016685:Mitomycin / Q000627:therapeutic use*; D051381:Rats
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D016685:Mitomycin; D000077146:Irinotecan; D002166:Camptothecin