S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis.
Br J Cancer
; 109(6): 1420-7, 2013 Sep 17.
Article
in En
| MEDLINE
| ID: mdl-23963147
ABSTRACT
BACKGROUND:
S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.METHODS:
Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m(-2) followed by oxaliplatin 85 mg m(-2) on day 1 and S-1 80 mg m(-2) per day from day 1 to 14 every 3 weeks. Polymorphisms in the UGT1A1, UGT1A6, UGT1A7 and CYP2A6 genes were analysed.RESULTS:
Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval 53.4-81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of UGT1A6*2 or UGT1A7*3 and an improved tumour response was noted in those without variant alleles of CYP2A6 or UGT1A1*60.CONCLUSION:
The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.
Full text:
1
Collection:
01-internacional
Health context:
3_ND
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
Type of study:
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2013
Document type:
Article