Docetaxel polymorphism

Isla, D., Sarries, C., Rosell, R., et al. (2004) Single nncleofide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-smaU-ceU lung cancer. Ann. Oncol. 15,1194-1203. 

P-gp is responsible for transport of the carboxylate form of irinotecan (64). The homozygous mutant 8 polymorphism has been associated with significantly increased exposure to irinotecan and its active metabolite SN-38 (65). Furthermore, significantly decreased docetaxel clearance was found in patients homozygous mutant for P-gp 8 (66), although Goh et al. (67) did not find a significant effect of this polymorphism on docetaxel pharmacokinetics. Also, a trend to an increased AUC of tipifamib in patients with the homozygous mutant allele compared to patients with only one or no mutant alleles of 8 was found in a study by Sparreboom et al. (68). In a study by Kishi et al. (40), the mutant allele for 6 was also correlated with a lower clearance of etoposide in children with ALL. 

Font A, Sanchez JM, Taron M et al. Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase lAl (UGTIAI) polymorphism. Invest New Drugs 2003 21 435 43. 

Mir O, Alexandre J, Tran A et al (2009) Relationship between GSTP1 Ile(105)Val polymorphism and docetaxel-induced peripheral neuropathy clinical evidence of a role of oxidative stress in taxane toxicity. Ann Oncol 20 736-740... 

---