Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients.
BACKGROUND
Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0-R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43 degrees C.


METHODS
A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43 degrees C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy.


RESULTS
Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001).


CONCLUSIONS
This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.
Elias
Dominique
D
Department of Surgical Oncology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, Cedex, France. elias@igr.fr
Goere
Diane
D
Blot
François
F
Billard
Valérie
V
Pocard
Marc
M
Kohneh-Shahri
Niaz
N
Raynard
Bruno
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016063:Blood Loss, Surgical; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002277:Carcinoma / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000601:surgery*; D011183:Postoperative Complications; D011446:Prospective Studies; D015996:Survival Rate; D059004:Topoisomerase I Inhibitors; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D000077150:Oxaliplatin; D014803:Vitamin B Complex; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin