Combination intraperitoneal chemotherapy is superior to mitomycin C or oxaliplatin for colorectal carcinomatosis in vivo.
BACKGROUND
Hyperthermic intraperitoneal (IP) chemotherapy after cytoreduction improves survival in patients with colorectal carcinomatosis of the peritoneal surface. Most protocols use single agents (mitomycin C or oxaliplatin) provided IP. The purpose of this study was to determine whether combination IP chemotherapy is superior to single-agent therapy in a mouse model.


METHODS
Nu/Nu mice were injected IP with HT-29 colorectal cancer cells. Animals were treated with single agents or combinations. Primary end point was overall survival. Agents explored included oxaliplatin, mitomycin C, panitumumab, erlotinib, cetuximab, and irinotecan delivered IP as single agents; mitomycin C, panitumumab, and irinotecan in combination IP; and 5-fluorouracil-leucovorin-irinotecan (FOLFIRI) in combination delivered intravenously.


RESULTS
Survival of mice receiving irinotecan or mitomycin C IP was greater than controls. Median survival of mice receiving intravenous FOLFIRI was also greater than control. However, survival of mice receiving IP irinotecan or mitomycin C was far greater than mice receiving intravenous FOLFIRI. For combination therapy, a positive interaction was observed with mitomycin C and irinotecan, whereas survival was greater than either agent individually. No interaction was observed between panitumumab and mitomycin C or irinotecan. However, an overall survival benefit was observed with the combination of irinotecan, mitomycin C, and panitumumab; at 120 days after cell injection, 100% of the triagent therapy group survived.


CONCLUSIONS
IP therapy with mitomycin C or irinotecan provided a survival benefit compared with intravenous FOLFIRI. Combination IP therapy with mitomycin C, panitumumab, and irinotecan was superior to all other agents tested alone or in combination. This warrants further combination analysis and supports consideration for a phase I application.
Cohen
Mark S
MS
Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
Al-Kasspooles
Mazin F
MF
Williamson
Stephen K
SK
Henry
David
D
Broward
Melinda
M
Roby
Katherine F
KF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D011799:Quinazolines; D000077150:Oxaliplatin; D016685:Mitomycin; D000077544:Panitumumab; D000077146:Irinotecan; D000069347:Erlotinib Hydrochloride; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin