Xeroderma pigmentosum group D haplotype predicts for response, survival, and toxicity after platinum-based chemotherapy in advanced nonsmall cell lung cancer.
BACKGROUND
The treatment of lung cancer has reached a therapeutic plateau. Several mechanisms of platinum resistance have been described, including the removal of platinum-DNA adduct by nucleotide excision repair (NER). Polymorphisms within the Xeroderma pigmentosum Group D protein (XPD), a member of the NER pathway, are associated with alterations in enzyme activity and may change sensitivity to platinum-based chemotherapy. The authors investigated the relation between XPD polymorphisms and treatment response, toxicity, and overall survival in patients who received platinum-based chemotherapy for advanced nonsmall cell lung cancer (NSCLC).


METHODS
Between 2001 and 2002, 108 patients with chemotherapy-naive, advanced NSCLC were recruited. Associations between XPD312/751 polymorphisms and XPD haplotype and treatment response, toxicity. and survival were evaluated.


RESULTS
Significant correlations were observed between XPD haplotype and Grade 4 neutropenia and overall survival together with a greater response to platinum-based chemotherapy for the XPD *A haplotype.


CONCLUSIONS
The XPD haplotype may represent a useful pharmacogenomic marker of platinum-based chemotherapy in patients with advanced NSCLC and requires prospective validation.
Booton
Richard
R
Christie Hospital National Health Service Trust, Manchester, United Kingdom. r.booton@btopenworld.com
Ward
Tim
T
Heighway
Jim
J
Taylor
Pat
P
Power
Fiona
F
Ashcroft
Linda
L
Morris
Julie
J
Thatcher
Nicholas
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004260:DNA Repair / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D015996:Survival Rate; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D009944:Organoplatinum Compounds; D051759:Xeroderma Pigmentosum Group D Protein