A National Cancer Institute of Canada Clinical Trials Group Study--IND.135: Phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer.
Thirty-one patients with metastatic colorectal cancer were enrolled in this phase I/II trial of a triple combination of camptosar (C), oxaliplatin (O) and tomudex (T), all given on day one of a convenient three-week schedule. Patients received 257 cycles (1-18) in five cohorts. Toxicity was manageable and haematological toxicity was mild to moderate. Diarrhoea was the main dose-limiting toxicity; nausea and vomiting were common. Fatigue was frequent, moderate in severity and a reason for discontinuation in some patients. The recommended phase II doses were (C) 220 mg/m(2), (O) 100mg/m(2), (T) 2.75 mg/m(2). A 50% response rate in 30 evaluable patients was confirmed by an independent radiology review board; progression-free survival and overall median survival were 7.3 months and 16.6 months, respectively. Of the 16 patients treated at the recommended dose, 9 (56.3%) experienced partial response. Further evaluation in a randomized study compared to sequential doublets is warranted. Triple combinations could be relevant in curative settings for high-risk patients.
Maroun
J A
JA
Medical Oncology, The Ottawa Hospital Regional Cancer Centre, 501 Smyth Road, Ottawa, Ont., Canada K1H 8L6. jmaroun@ottawahospital.on.ca
Jonker
D
D
Seymour
L
L
Goel
R
R
Vincent
M
M
Kocha
W
W
Cripps
C
C
Fisher
B
B
Lister
D
D
Malpage
A
A
Chiritescu
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002170:Canada; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; D000077146:Irinotecan; C068874:raltitrexed; D002166:Camptothecin