Clinical outcome of gemcitabine (gem)/cisplatin (cis)- vs docetaxel (doc)/cis-treated stage IV non-small cell lung cancer (NSCLC) patients (p) according to X-ray repair cross-complementing group 3 (XRCC3) polymorphism and age

• Published in: Journal of clinical oncology Vol. 24; no. 18_suppl; p. 7055
• Main Authors: Rosell-Costa, R., Alberola, V., Camps, C., Lopez-Vivanco, G., Moran, T., Etxaniz, O., De Las Peñas, R., Gupta, J., Taron, M., Sanchez, J.
• Format: Journal Article
• Language: English
• Published: 20.06.2006
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2006.24.18_suppl.7055

Abstract only 7055 Background: Significant interaction between XRCC1 genotype and age has been reported, with younger subjects having a greater risk of developing lung cancer. Carriers of XRCC3 241 MetMet have higher levels of DNA adducts, leading us to hypothesize that they would be more chemosensitive, especially younger patients. Methods: Real-time PCR assay was used to determine XRCC3 genotype from DNA isolated from baseline blood samples of 878 stage IV NSCLC p (162 treated with gem/cis; 716 with doc/cis). Median age, 60; 266 p (30%) <55; 239 p (39%) 55–66; 273 p (31%) >66. Adenocarcinoma: 459 p (53%). Homozygous variant XRCC3 241 MetMet was found in 124 p (14%), with the same frequency in each of the three age groups. Results: After a median follow-up of 7.6 months (m) (95% CI, 1–47 m), overall median survival (MS) was 9.5 m (95% CI, 8.8–10.2 m), with no differences between the 2 regimens. In all p with XRCC3 241 MetMet, MS was 12.9 m for p treated with gem/cis and 8.4 m for p treated with doc/cis (P = 0.06) (hazard ratio at 2 y = 0.23). In p with XRCC3 241 MetMet <55 y, MS was not reached for p treated with gem/cis and 9.2 m for p treated with doc/cis (P = 0.02), which translated into a 60% difference in survival at 2 y. This difference diminished in p with XRCC3 241 MetMet 55–66 y (MS 12.9 m with gem/cis, 6.9 m with doc/cis [P = 0.09]; 28% difference in survival at 2 y) and disappeared in p >66 y (MS 5.8 m with gem/cis, 7.8 m with doc/cis [P = 0.55]. For the other XRCC3 241 genotypes (ThrThr and ThrMet), no differences in MS were found either overall or broken down by age. Conclusions: XRCC3 241 MetMet is both an easily assessable and robust predictive marker for survival in younger gem/cis-treated NSCLC p. The survival benefit dwindles with increasing age, possibly related to the enhanced DNA repair capacity of older p. No significant financial relationships to disclose.