ERCC1 and ERCC2 Polymorphisms Predict the Efficacy and Toxicity of Platinum-Based Chemotherapy in Small Cell Lung Cancer
Por:
Barba, A, López-Vilaró, L, Ferre, M, Majem, M, Martinez-Recio, S, Bell, O, Arranz, MJ, Salazar, J, Sullivan, I
Publicada:
1 sep 2024
Resumen:
Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination. Despite a high objective response rate, responses are not durable and chemotherapy-induced toxicity may compromise treatment. Genetic variants in genes involved in the DNA-repair pathways and in etoposide metabolization could predict treatment efficacy and safety and help personalize platinum-based chemotherapy. Germline polymorphisms in XRCC1, ERCC1, ERCC2, ABCB1, ABCC3, UGT1A1 and GSTP1 genes were investigated in 145 patients with SCLC. The tumor expression of ERCC1 was determined using immunohistochemistry, and the tumor expression of ERCC1-XPF was determined via a proximity ligation assay. Survival analyses showed a statistically significant association between the ERCC1 rs11615 variant and median progression-free survival (PFS) in patients with limited-stage (LS) SCLC (multivariate: hazard ratio 3.25, [95% CI 1.38-7.70]; p = 0.007). Furthermore, we observed differences between the ERCC1-XPF complex and median PFS in LS-SCLC, although statistical significance was not reached (univariate: positive expression 10.8 [95% CI 4.09-17.55] months versus negative expression 13.3 [95% CI 7.32-19.31] months; p = 0.06). Safety analyses showed that the ERCC2 rs1799793 variant was significantly associated with the risk of grade >= 3 thrombocytopenia in the total cohort (multivariate: odds ratio 3.15, [95% CI 1.08-9.17]; p = 0.04). Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed.
Filiaciones:
Barba, A:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Univ Autonoma Barcelona, Fac Med, Dept Med, Barcelona 08035, Spain
López-Vilaró, L:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08041, Spain
Ferre, M:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08041, Spain
Majem, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Martinez-Recio, S:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Bell, O:
Inst Recerca St Pau IR St Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
Arranz, MJ:
Fundacio Docencia & Recerca Mutua Terrassa, Res Lab Unit, Terrassa 08221, Spain
Salazar, J:
Inst Recerca St Pau IR St Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
Sullivan, I:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
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