e14515 Background: Peripheral neuropathy (PNP) is a dose-limiting side effect of oxaliplatin based chemotherapy. High grade PNP may compromise quality of life especially in elderly patients (pts). A randomized multicenter phase II study was conducted to compare fluorouracil, leucovorin, oxaliplatin with or without docetaxel (FLO vs. FLOT, respectively) in elderly pts with advanced gastric cancer (AGC). Our purpose was to identify pharmacogenetic markers as predictors of high grade PNP within this study. Methods: 143 pts were enrolled in this study. Pts. were numerically >65 years or numerically >59 years but classified biologically >65 years as defined by an Instrumental Activities of Daily Living score of <8. PNP was classified according to an oxaliplatin specific scale. Genotyping was performed using PCR-based RFLP or TaqMan®-based allelic discrimination. 20 polymorphisms in 13 genes being part of the metabolism of the applied drugs or DNA repair were analyzed. Statistical analyses were based on stepwise multivariate cox regression models and included genotypes and clinical parameters. Results: Median age was 71 years (range 60–83). Pts received in median 6 cycles of treatment (range 1–12). 130 pts were evaluable for PN at time of analyses. Of these, 68 received FLO and 62 received FLOT. Cumulative grade 3 PNP occurred in 49% of pts without a significant difference between FLO and FLOT receiving pts (44% and 53%, respectively, p=0.4). Genotypes of TS and MTHFR could be identified as independent risk factors for grade 3 PNP by multivariate analyses. Pts carrying a TS promoter genotype known to be associated with low TS expression (2R/2R, 2R/3RC, 3RC/3RC) were at higher risk for developing grade 3 PNP compared to pts without one of these genotypes (OR 3.0 [95%CI 1.27; 7.06], p=0.01). Pts carrying MTHFR1298AC or CC genotypes were also at higher risk for experiencing grade 3 PNP compared to pts with the wildtype MTHFR-1298AA genotype (OR 3.1 [95%CI 1.26; 7.60], p=0.01). In fact, 89% of pts that experienced grade 3 PNP were carriers of at least one of these risk genotypes. Conclusions: Polymorphisms of TS and MTHFR might be associated with grade 3 PNP in AGC pts receiving oxaliplatin based chemotherapy. No significant financial relationships to disclose.
Efficacy of locally endoscopic cytoreductive surgery in elderly patients with advanced gastric cancer