US patients treated with 5FU or Xeloda® (capecitabine) were more likely to experience serious side effects than patients outside the United States. They also required more dose reductions and had to stop treatment more often than their non-US counterparts.
Researchers reviewed the safety results of three randomized phase III clinical trials comparing bolus regimens of 5FU to Xeloda (capecitabine) to treat metastatic cancer, separating enrolled patients into those treated in the United States and those treated in other parts of the world. They also analyzed an adjuvant trial that included US patients, patients in East Asia, and patients in the rest of the world. Infusional 5FU was not part of any of these studies.
In the metastatic trials, US patients were about 75 percent more likely to experience a serious adverse event. Their relative risk of a grade 3 or 4 side effect was 1.77 compared to patients in other parts of the world. Side effects included gastrointestinal (diarrhea, nausea, vomiting, and mouth sores), lowered white cell counts and infections, and hand-and-foot syndrome.
US patients also had to have chemotherapy doses reduced about 72 percent more often, and they discontinued treatment about 83 percent more frequently.
In the adjuvant trial, US patients also had the highest rate of adverse events. Patients in East Asia had the lowest.
In trying to understand the differences, the research team considered:
- Differences in how doctors or patients perceive and report side effects and how willing they may be to continue treatment despite them
- Ethnic influences that include both biological differences and the impact of culture on factors such as diet.
- The use of folate supplementation in the United States. In other studies, higher levels of folate in the blood before chemotherapy began have meant worse side effect.
In concluding, Daniel Haller, M.D. and his colleagues wrote,
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 metastatic colorectal cancer 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, relative rates.
SOURCE: Haller et al., Journal of Clinical Oncology, Volume 26, Number 13, May 1, 2008.