Potential regional differences for the tolerability profiles of fluoropyrimidines.

• 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 multivariate analysis: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

Antimetabolites

Antineoplastic

administration & dosage

adverse effects

Antineoplastic Combined Chemotherapy Protocols

adverse effects

Chemotherapy

Adjuvant

Colorectal Neoplasms

drug therapy

ethnology

pathology

Deoxycytidine

administration & dosage

adverse effects

analogs & derivatives

Europe

Far East

Fluorouracil

administration & dosage

adverse effects

analogs & derivatives

Gastrointestinal Diseases

chemically induced

ethnology

Humans

Leucovorin

administration & dosage

Neoplasm Metastasis

Neutropenia

chemically induced

ethnology

Organoplatinum Compounds

administration & dosage

Prodrugs

administration & dosage

adverse effects

Residence Characteristics

Retrospective Studies

Risk Assessment

Severity of Illness Index

Treatment Outcome

United States

Vitamin B Complex

administration & dosage

Withholding Treatment

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