670P - Effect of degradation rate of 5-FU and genetic polymorphisms of DPD, TSER and MTHRF on toxicity and survival of 5-FU-based chemotherapy in gastric...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Complications of Treatment
Pharmacology
Gastric Cancer
Presenter Federica Mazzuca
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors F. Mazzuca, A. Botticelli, L. Lionetto, M. La Torre, R. Giusti, C. Maddalena, P. Pellegrini, G. Gentile, F.R. Ciabatta, M. Borro, V. Ziparo, M. Simmaco, P. Marchetti
  • Oncologia Medica, Azienda Ospedaliera Sant'Andrea - " Sapienza" Facoltà di Medicina e Psicologia, 00189 - Roma/IT

Abstract

Aim

5-FU based chemotherapy is the most common regimen used for patients affected by gastric cancer both in metastatic and in adjuvant setting.Identification of predictive markers of both response and toxicity to chemotherapy is a promising approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FU-DR) and genetic polymorphisms (MTHFR, TSER, DPYD) on predicting toxicity to chemotherapy and survival

Methods

94 patients affected by gastric cancer were enrolled. Genetic polymorphisms of MTHFR, TSER and DPYD and the 5-FU-DR were analyzed. 5-FU degradation rate was determined by measuring the decrease of a fixed amount of 5-FU (10 [mu]g/mL) added to a solution of PBMC, after 2 hours incubation, expressed as nanogram per milliliter of 5-FU degraded per minute x 106 cells.Gene polymorphisms ofMTHFR, DPYD and TSER were analysed by pyrosequensing of genomic DNA extracted from peripheral blood samples. Genetic markers and the 5-FU-DR were correlated with clinical response, survival and toxicity to treatment.

Results

We enrolled 94 patients with gastric adenocarcinoma. All of them received 5FU-based chemotherapy : 39 patients in metastatic setting (28 males and 11 females) and 55 in adjuvant setting (36 males and 19 females). Among the 55 patients in adjuvant setting, 44 of them developed grade 1 and 2 toxicities, while 11 patients developed grade 3 or 4 toxicities. Among the 39 patients treated for metastatic disease, 29 patients reported grade 1 or 2 toxicities while 10 reported toxicities of grade 3 and 4. We didn't found any association between polymorphisms, 5FU-DR and toxicities. We demonstrated a statistically significant association between the polymorphism of DPYD and 5FUDR (p = 0.01). In terms of survival, patients poor metabolizer with a 5-FU-DR < 1.35 ng/mL/min showed a better overall survival compared to those with a 5-FU-DR ≥ 1.35 ng/mL/min (p = 0.04).

Conclusions

5-FU-DR and genetic polymorphisms of MTHFR and DPYD seem to be significantly involved in survival of patients undergone 5-FU based CHT for gastric cancer both in metastatic and adjuvant setting. Although, the small sample size of patients enrolled in the study, our results suggest that identification of predictive markers of toxicities and survival could help in providing a tailored treatment in patients affected by gastric cancer.

Disclosure

All authors have declared no conflicts of interest.