5-Fluorouracil Degradation Rate in Patients with Recurrent Gastrointestinal Cancer Treated with Metronomic Capecitabine

Date 29 June 2016
Event ESMO World Congress on Gastrointestinal Cancer 2016
Session ESMO World Congress on Gastrointestinal Cancer 2016 - Abstracts book
Presenter M. Roberto
Citation Annals of Oncology (2016) 27 (2): 1-85. 10.1093/annonc/mdw199
Authors M. Roberto1, A. Romiti1, L. Lionetto2, C. D'Antonio1, C. Onesti3, A. Botticelli3, A. Milano1, R. Falcone3, M. Occhipinti3, F. Mazzuca3, M. Simmaco4, P. Marchetti1
  • 1La Sapienza University, Sant'Andrea Hospital, Rome, Italy, /
  • 2Istituto Dermopatico dell'Immacolata, Rome, Italy, /
  • 3University La Sapienza, Sant'Andrea Hospital, Rome, Italy, /
  • 4University La Sapienza, Rome, Italy, /

Abstract

5-Fluoruracil (5-FU) is the milestone chemotherapeutic drug for the treatment of the gastrointestinal tract (GI) tumours. Dihydropyrimidine dehydrogenase (DPD) is the key enzyme involved in 5-FU catabolism. DPD deficiency may often subtend the development of severe toxicities in patients treated with a fluoropyrimidine-based chemotherapy. The degradation rate of 5-FU is a phenotypic marker of the 5-FU metabolism. We have recently described a correlation between DPD gene (DPYD) polymorphism and 5-FU degradation rate [1]. Moreover, patients with altered 5-FU degradation rate showed high prevalence of severe toxicities after a fluoropyrimidine-based chemotherapy [2]. Thus, 5-FU degradation rate has been suggested as a putative biomarker of 5-FU fluorouracil toxicity. In detail, patients with a value below the 5th centile (poor metabolism - PM) or above the 95th centile (ultra-rapid metabolism - UM) experienced a higher incidence of grade 3-4 toxicity compared with those patients whose 5-FU degradation rate was within 5-95th centile (0.85-2.2 ng/ml/106 cells/min).

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Data about 5-FU degradation rate and outcome of metronomic capecitabine (mCAP) in patients with GI cancer are still lacking. The aim of the study was to explore the relationship between the 5-FU degradation rate and toxicity of low dose capecitabine in pretreated patients with GI cancer.