Literature DB >> 22754590

Tegafur-uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle.

Daniel I G Cubero1, Felipe Melo Cruz, Patrícia Santi, Ismael Dale C G Silva, Auro Del Giglio.   

Abstract

OBJECTIVE: The objective of this study was to evaluate the safety of using tegafur-uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. PATIENTS AND METHODS: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m(2)/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle.
RESULTS: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea).
CONCLUSION: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

Entities:  

Keywords:  colorectal neoplasms; dihydropyrimidine dehydrogenase deficiency; drug toxicity; fluorouracil; tegafur; uracil

Year:  2012        PMID: 22754590      PMCID: PMC3384092          DOI: 10.1177/1758834012441049

Source DB:  PubMed          Journal:  Ther Adv Med Oncol        ISSN: 1758-8340            Impact factor:   8.168


  32 in total

1.  Semi-automated radioassay for determination of dihydropyrimidine dehydrogenase (DPD) activity. Screening cancer patients for DPD deficiency, a condition associated with 5-fluorouracil toxicity.

Authors:  M R Johnson; J Yan; L Shao; N Albin; R B Diasio
Journal:  J Chromatogr B Biomed Sci Appl       Date:  1997-08-29

2.  Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients.

Authors:  Hany H Ezzeldin; Adam M Lee; Lori K Mattison; Robert B Diasio
Journal:  Clin Cancer Res       Date:  2005-12-15       Impact factor: 12.531

3.  Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06.

Authors:  Barry C Lembersky; H Samuel Wieand; Nicholas J Petrelli; Michael J O'Connell; Linda H Colangelo; Roy E Smith; Thomas E Seay; Jeffrey K Giguere; M Ernest Marshall; Andrew D Jacobs; Lauren K Colman; Atilla Soran; Greg Yothers; Norman Wolmark
Journal:  J Clin Oncol       Date:  2006-05-01       Impact factor: 44.544

4.  Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5-FU-based chemotherapy.

Authors:  Laia Paré; David Paez; Juliana Salazar; Elisabeth Del Rio; Eduardo Tizzano; Eugenio Marcuello; Montserrat Baiget
Journal:  Br J Clin Pharmacol       Date:  2010-08       Impact factor: 4.335

5.  Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer.

Authors:  M M Borner; P Schoffski; R de Wit; F Caponigro; G Comella; A Sulkes; G Greim; G J Peters; K van der Born; J Wanders; R F de Boer; C Martin; P Fumoleau
Journal:  Eur J Cancer       Date:  2002-02       Impact factor: 9.162

6.  Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.

Authors:  P Piedbois; P Rougier; M Buyse; J Pignon; L Ryan; R Hansen; B Zee; B Weinerman; J Pater; C Leichman; J Macdonald; J Benedetti; J Lokich; J Fryer; G Brufman; R Isacson; A Laplanche; E Levy
Journal:  J Clin Oncol       Date:  1998-01       Impact factor: 44.544

7.  Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group.

Authors:  P C Simmonds
Journal:  BMJ       Date:  2000-09-02

8.  Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians.

Authors:  Lori Kay Mattison; Jeanne Fourie; Renee A Desmond; Anil Modak; Muhammad Wasif Saif; Robert B Diasio
Journal:  Clin Cancer Res       Date:  2006-09-15       Impact factor: 12.531

9.  Cancer statistics, 2009.

Authors:  Ahmedin Jemal; Rebecca Siegel; Elizabeth Ward; Yongping Hao; Jiaquan Xu; Michael J Thun
Journal:  CA Cancer J Clin       Date:  2009-05-27       Impact factor: 508.702

10.  Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.

Authors:  Amanda C Ashley; Daniel J Sargent; Steven R Alberts; Axel Grothey; Megan E Campbell; Roscoe F Morton; Charles S Fuchs; Ramesh K Ramanathan; Stephen K Williamson; Brian P Findlay; Henry C Pitot; Richard M Goldberg
Journal:  Cancer       Date:  2007-08-01       Impact factor: 6.860

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  2 in total

1.  Tegafur-uracil (UFT) in lower doses is safe for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle.

Authors:  Daniel I G Cubero; Auro Del Giglio
Journal:  Ther Adv Med Oncol       Date:  2013-01       Impact factor: 8.168

2.  Standard-dose tegafur-uracil (UFT) is not a safe alternative in partial dihydropyrimidine dehydrogenase-deficient patients.

Authors:  Maarten J Deenen; Annemieke Cats; Jos H Beijnen; Jan H M Schellens
Journal:  Ther Adv Med Oncol       Date:  2013-01       Impact factor: 8.168

  2 in total

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