PURPOSE: Polymorphisms that are associated with ABCB1 expression and function may be linked to treatment efficacy and the development of neutropenia and neurotoxicity in patients with androgen-independent prostate cancer receiving docetaxel. EXPERIMENTAL DESIGN: Patients with androgen-independent prostate cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n = 50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by direct sequencing, and diplotypes were constructed using an EM algorithm. The data were then compared with duration to onset of peripheral neuropathy, neutropenia grade, and survival after docetaxel. RESULTS: For patients receiving docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G-3435C linked alleles had improved overall survival after treatment (P = 0.0017). Additionally, patients treated with docetaxel and thalidomide carrying a diplotype consisting of the 2677T-3435T haplotype had a shorter median survival (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel and thalidomide cohort. Among both treatment arms together, individuals carrying the 2677GG genotype also had a significantly longer time to neuropathy (P = 0.035). Finally, there was a strong trend toward patients carrying the 2677TT-3435TT diplotype having higher grades of neutropenia (P = 0.053). CONCLUSION: The data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants with ensuing negative implications for docetaxel treatment in patients carrying ABCB1 variant genotypes.
PURPOSE: Polymorphisms that are associated with ABCB1 expression and function may be linked to treatment efficacy and the development of neutropenia and neurotoxicity in patients with androgen-independent prostate cancer receiving docetaxel. EXPERIMENTAL DESIGN:Patients with androgen-independent prostate cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n = 50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by direct sequencing, and diplotypes were constructed using an EM algorithm. The data were then compared with duration to onset of peripheral neuropathy, neutropenia grade, and survival after docetaxel. RESULTS: For patients receiving docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G-3435C linked alleles had improved overall survival after treatment (P = 0.0017). Additionally, patients treated with docetaxel and thalidomide carrying a diplotype consisting of the 2677T-3435T haplotype had a shorter median survival (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel and thalidomide cohort. Among both treatment arms together, individuals carrying the 2677GG genotype also had a significantly longer time to neuropathy (P = 0.035). Finally, there was a strong trend toward patients carrying the 2677TT-3435TT diplotype having higher grades of neutropenia (P = 0.053). CONCLUSION: The data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants with ensuing negative implications for docetaxel treatment in patients carrying ABCB1 variant genotypes.
Authors: Tessa M Bosch; Alwin D R Huitema; Valerie D Doodeman; Robert Jansen; Els Witteveen; Wim M Smit; Rob L Jansen; Carla M van Herpen; Marcel Soesan; Jos H Beijnen; Jan H M Schellens Journal: Clin Cancer Res Date: 2006-10-01 Impact factor: 12.531
Authors: F M Molloy; M K Floeter; N A Syed; F Sandbrink; E Culcea; S M Steinberg; W Dahut; J Pluda; E A Kruger; E Reed; W D Figg Journal: Muscle Nerve Date: 2001-08 Impact factor: 3.217
Authors: A Tran; V Jullien; J Alexandre; E Rey; F Rabillon; V Girre; V Dieras; G Pons; F Goldwasser; J M Tréluyer Journal: Clin Pharmacol Ther Date: 2006-05-02 Impact factor: 6.875
Authors: Tristan M Sissung; Klaus Mross; Seth M Steinberg; Dirk Behringer; William D Figg; Alex Sparreboom; Stephan Mielke Journal: Eur J Cancer Date: 2006-09-06 Impact factor: 9.162
Authors: Ian F Tannock; Ronald de Wit; William R Berry; Jozsef Horti; Anna Pluzanska; Kim N Chi; Stephane Oudard; Christine Théodore; Nicholas D James; Ingela Turesson; Mark A Rosenthal; Mario A Eisenberger Journal: N Engl J Med Date: 2004-10-07 Impact factor: 91.245
Authors: Tristan M Sissung; Sarah M Troutman; Tessa J Campbell; Heather M Pressler; Hyeyoung Sung; Susan E Bates; William D Figg Journal: Discov Med Date: 2012-01 Impact factor: 2.970
Authors: John F Deeken; Rebecca Slack; Glen J Weiss; Ramesh K Ramanathan; Michael J Pishvaian; Jimmy Hwang; Karen Lewandowski; Deepa Subramaniam; Aiwu Ruth He; Ion Cotarla; Aquilur Rahman; John L Marshall Journal: Cancer Chemother Pharmacol Date: 2012-12-30 Impact factor: 3.333
Authors: Ilaria Pastina; Elisa Giovannetti; Aldo Chioni; Tristan M Sissung; Francesco Crea; Cinzia Orlandini; Douglas K Price; Claudia Cianci; William D Figg; Sergio Ricci; Romano Danesi Journal: BMC Cancer Date: 2010-09-27 Impact factor: 4.430
Authors: Lokesh Jain; Tristan M Sissung; Romano Danesi; Elise C Kohn; William L Dahut; Shivaani Kummar; David Venzon; David Liewehr; Bevin C English; Caitlin E Baum; Robert Yarchoan; Giuseppe Giaccone; Jürgen Venitz; Douglas K Price; William D Figg Journal: J Exp Clin Cancer Res Date: 2010-07-14