Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan.
OBJECTIVE
A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan.


METHODS
DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression.


RESULTS
No associations were observed.


CONCLUSIONS
Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m2.
Hoskins
Janelle M
JM
UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Genetic Medicine Building, Chapel Hill, NC 27599-7360, USA. janelle_hoskins@unc.edu
Rosner
Gary L
GL
Ratain
Mark J
MJ
McLeod
Howard L
HL
Innocenti
Federico
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006239:Haplotypes / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009503:Neutropenia / Q000139:chemically induced / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*; D012307:Risk Factors
D000077146:Irinotecan; D002166:Camptothecin