Differences between Asians & Caucasians in chemotherapeutic related outcomes in patients with colorectal cancer

Abstract

Aim: The overall aim of this study was to test the hypothesis that Asians will differ from Caucasians in their outcomes from chemotherapeutic agents based on likely inter-racial differences in the frequencies of genotypes related the chemotherapeutic related outcomes.Materials and Methods: This thesis in divided into two studies. In the first study (review), published literature was searched to identify genotypes associated with outcomes in patients receiving agents involved colorectal cancer chemotherapy. Frequencies of the identified genotypes in healthy Asian and Caucasian populations were then annotated from published studies and chemotherapy-related outcomes for Asians inferred from the outcome association of given genotypes and their frequency in Asians compared to Caucasians. In the second study, frequencies of diarrhea, nausea and vomiting, stomatitis and response and survival rates were collated from reports on Phase II trials involving FP (5-fluorouracil, capecitabine, UFT, S-1)-based treatment. The respective frequencies in the two races were summarized by meta-analytical methods and differences compared to hypothetical outcome differences generated by the first study.Results: Literature review identified 11 prominent genes linked to outcome from fluoropyrimdine, irinotecan or oxaliplatin-based treatment. Marked differences in the frequencies of many of these were observed between Asians and Caucasians. Based on some genotypes, Asians could be expected to experience lower toxicity and shorter survival times from fluoropyimidines, and lower toxicity from irinotecan. Both worse and improved outcome prospects from oxaliplatin-based chemotherapy are implied depending on the genotype examined. The meta-analysis showed Asians compared to Caucasians to experience significantly less toxicity (diarrhea, nausea and vomiting and stomatitis) from FP treatment but have no differences in response or survival rates, although there was a significant heterogeneity between studies.Conclusion: Asians differ from Caucasians in their outcomes from chemotherapeutic agents in a manner potentially predictable from inter-racial differences in chemotherapy outcome-linked genotypes. These differences however could be restricted to host (toxicity) and not tumour (response or survival) characteristics.