Potential regional differences for the tolerability profiles of fluoropyrimidines.
J Clin Oncol
; 26(13): 2118-23, 2008 May 01.
Article
in En
| MEDLINE
| ID: mdl-18445840
ABSTRACT
PURPOSE:
We conducted a retrospective analysis of safety data from randomized, single-agent fluoropyrimidine clinical trials (bolus fluorouracil/leucovorin [FU/LV] and capecitabine) to test the hypothesis that there are regional differences in fluoropyrimidine tolerability.METHODS:
Treatment-related safety data from three phase III clinical studies were analyzed by multivariateanalysis:
two comparing capecitabine with bolus FU/LV in metastatic colorectal cancer (MCRC) and one comparing capecitabine plus oxaliplatin (XELOX) with bolus FU/LV as adjuvant treatment for colon cancer. The United States (US) was compared with non-US countries (all three studies) and with the rest of the world and East Asia (adjuvant study).RESULTS:
In the MCRC studies (n = 1,189), more grade 3/4 adverse events (AEs; relative risk [RR], 1.77), dose reductions (RR, 1.72), and discontinuations (RR, 1.83) were reported in US versus non-US patients. Likewise, in the adjuvant colon cancer study (n = 1,864), more grade 3/4 AEs (RR, 1.47) and discontinuations (RR, 2.09) were reported in US versus non-US patients. After further dividing non-US patients into those in East Asia and the rest of the world, differential RRs for related grade 3/4 AEs, grade 4 AEs, and serious AEs were again observed, with East Asian patients having the lowest and US patients the highest RR.CONCLUSION:
Regional differences exist in the tolerability profiles of fluoropyrimidines. More treatment-related toxicity was reported in the US compared with the rest of the world for bolus FU/LV and capecitabine in first-line MCRC and adjuvant colon cancer. In the adjuvant setting, a range of fluoropyrimidine tolerability was observed, with East Asian patients having the lowest, and US patients the highest, RR.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Colorectal Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
/
Deoxycytidine
/
Fluorouracil
/
Gastrointestinal Diseases
/
Antimetabolites, Antineoplastic
/
Neutropenia
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Aspects:
Patient_preference
Limits:
Humans
Country/Region as subject:
America do norte
/
Asia
/
Europa
Language:
En
Journal:
J Clin Oncol
Year:
2008
Document type:
Article
Affiliation country:
United States