Genetic polymorphisms of SCNA9 as predictive markers of oxaliplatin-induced neuropathy

9073 Background: Oxaliplatin (OXL) is an active drug in digestive tumors. Oxaliplatin induced peripheral neuropathy (OIN) is the main dose limiting toxicity. Around 60-80% of patients developed a mild cold-induced neurotoxicity that used to disappear few days after but in 15% became a persistent neuropathy. The pathophysiology of oxaliplatin-induced neuropathy (OIN) remains unclear, preclinical studies suggest involvement of voltage Na channels. SCN9A gene codifies to Na channels α subunit highly expressed in nociceptive neurons. Mutations in SCN9A are involved in alterations in neuropatic pain perception. This study tried to identify if variants in SCN9A could be associated to a higher risk to OIN. Methods: Serum were obtained from 100 patients with digestive cancer (colorectal, gastric, pancreatic and bile duct) treated with OXL (adjuvant or advanced setting) in Infanta Sofía University Hospital. No diabetes or hypotiroidism were detected. Patients were divided in two groups according to the development of OIN: Arm A 50 patients diagnosed of grade 2-3 OIN after 6 courses and Arm B 50 with no OIN. The evaluation of severity of the OIN by a neurologist included a classification according to NCI-CTC and OSNS scales and conduction studies. Genomic DNA was isolated from serum and variants of SCN9A were analyzed by PCR-RFLP. The relation between SCN9A genotype and the development of severe OIN was the primary aim Results: One hundred patients were enrolled between May 2010-November 2011. 56 (56%) females and 44 (44%) males; mean age was 62; mean ECOG was 1; primary tumor were colorectal 81 pts (81%), gastric 10 (10%); 8 (8%) pancreto-biliar and anus 1(1%). Stage were classified in localized 65 (65%) and advanced (35%). The chemotherapy regimen included: 94 (94%) XELOX, 1 (1%) XELOX-Herceptin and 5 (5%) EOX regimen. The mean of cycles were 7 (1-14). Mean OXL dose intensity was 100mg/m2.The mean PFS was 23 months. High expression of SCN9A variants were detected in patients 26/50, 52% arm A and in 5/50, 10% arm B patients, suggesting a possible relationship beetwen the development of OIN and SCN9A genotype (p=0.04). Conclusions: SCN9A polimorphysms may help to identify those patients with a higher risk to develop oxaliplatin induced neuropathy.