Background: Retrospective analyses suggested that a pharmacogenetic approach may allow a tailored selection of chemotherapy for metastatic colorectal cancer. Aim: We conducted a phase II study of pharmacogenetic-selected first-line chemotherapy in elderly patients with advanced colorectal cancer, with the aim to improve efficacy and to reduce toxicity in this group of patients. Methods: 24 patients were enrolled in this study. Chemotherapy regimen was prospectively assigned based on TS, DPD, ERCC-1 and UGT1A1 genotyping results. Twelve patients (50%) were treated with modified FOLFIRI, 11 patients (46%) with modified FOLFOX6 and 1 (4%) with De Gramont regimen. Results: A partial remission was obtained in 4 cases (17%), stable disease in 8 cases (33%) and progressive disease in 12 cases (50%). Grade 3-4 neutropenia was observed in 7 patients (29%) and diarrhoea in 3 cases (12%). The trial was then interrupted according to study design requiring 13 partial remissions out of the first 24 patients enrolled as the necessary response rate level in order to continue. Conclusion: Prospective selection of chemotherapy based on TS, DPD, ERCC-1 and UGT1A1 expression in elderly advanced colorectal cancer patients failed to confirm previous results. A more accurate validation of retrospective findings is warranted before these molecular markers can be used for treatment selection in the clinical practice.
Phase II study of pharmacogenetic-tailored therapy in elderly colorectal cancer patients / M. Scartozzi, C. Loretelli, R. Berardi, C. Pierantoni, R.R. Silva, D. Mari, R. Giampieri, L. Faloppi, M. Pistelli, E. Maccaroni, A. Bittoni, M. Del Prete, E. Galizia, S. Cascinu. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - 44:1(2012 Jan), pp. 74-79.
|Titolo:||Phase II study of pharmacogenetic-tailored therapy in elderly colorectal cancer patients|
|Parole Chiave:||DPD; ERCC-1; TS; UGT1A1; aged; aged, 80 and over; antineoplastic combined chemotherapy protocols; colorectal neoplasms; DNA-binding proteins; Dihydrouracil Dehydrogenase (NADP); endonucleases; female; genotyping techniques; glucuronosyltransferase; humans; male; thymidylate synthase; treatment outcome; pharmacogenetics; hepatology; gastroenterology|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
Settore MED/04 - Patologia Generale
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/13 - Biologia Applicata
Settore MED/03 - Genetica Medica
|Data di pubblicazione:||gen-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.dld.2011.08.006|
|Appare nelle tipologie:||01 - Articolo su periodico|
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