Dilemma of dihydropyrimidine dehydrogenase deficiency in colorectal cancer patients: is Uftoral® the right answer?

2014 ◽  
Vol 3 (4) ◽  
pp. 315-319 ◽  
Author(s):  
Sameer Rastogi ◽  
Bhawna Sirohi ◽  
Kedar Deodhar ◽  
Nitin Shetty ◽  
Shailesh V Shrikhande
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Dihydropyrimidine Dehydrogenase Deficiency

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

2012 ◽  
Vol 4 (4) ◽  
pp. 167-172 ◽  
Author(s):  
Daniel I.G. Cubero ◽  
Felipe Melo Cruz ◽  
Patrícia Santi ◽  
Ismael Dale C.G. Silva ◽  
Auro del Giglio
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
Gene Sequencing ◽  
Severe Toxicity ◽  
Safe Alternative ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Proof Of Principle

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/m2/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.

scholarly journals Dihydropyrimidine Dehydrogenase Gene Variation and Its Association with 5-Fluorouracil Toxicity in Colorectal Patients

2018 ◽  
Vol 3 (3) ◽  
pp. 65-69
Author(s):  
Ebrahim Salehifar ◽  
Mohammad Javad Abd Haghighi ◽  
Reza Negarandeh ◽  
Ghasem Janbabai ◽  
Fatemeh Safgafi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Dihydropyrimidine Dehydrogenase ◽  
Venous Blood ◽  
Critical Role ◽  
Optimization Method ◽  
Gene Variation ◽  
North Of Iran ◽  
Colorectal Cancer Patients

Objective: Dihydropyrimidine dehydrogenase (DPD), an enzyme translated by DPD gene (DPYD), has a critical role in the metabolism of 5-fluorouracil (5FU). In this study we aimed to investigate the frequency of the IVS14+1 G>A, 2194G>A, 2846 A>T mutations in the DPYD gene in colorectal cancer patients in north of Iran and their association with side effects of 5FU.Methods: Venous blood samples of 89 colorectal cancer patients were drawn. After the DNA extraction from nuclear cells, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the frequency of the IVS14+1 G>A and 2846 A>T mutations. Tetra-Primer ARMS PCR optimization method was used to detect the 2194 G>A mutation. Side effects were classified according to CTCAE (common terminology criteria for adverse events V. 4) and the association between different polymorphisms and side effects were evaluated.Results: Of 89 colorectal patients, the frequency of IVS14+1 G>A and 2846 A>T polymorphism was 4 (5.1%) and 1 (1.1%), respectively. The 2194 G>A polymorphism was not detected. All 4 patients were heterozygous for IVS14+1 G>A mutation, whereas the only patient with 2846 A>T polymorphism was homozygous. Some adverse effects of 5FU including diarrhea, vomiting, mucositis and stomatitis were more frequent in patients with IVS14+1 G>A polymorphism.Conclusion: The prevalence of IVS14+1 G>A mutation in our patients were relatively high and was associated with a higher occurrence of 5FU-associated toxicities.

The 2-13C-5-fluorouracil breath test (FUBT) as a novel, rapid method for assessment of dihydropyrimidine dehydrogenase (DPD) activity in cancer patients: Initial characterization and comparison to the 2-13C-uracil breath test (UraBT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2551-2551
Author(s):  
J. Fourie ◽  
L. K. Mattison ◽  
T. E. Wood ◽  
J. A. Posey ◽  
A. Modak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Dose ◽  
Oral Dose ◽  
Cancer Patients ◽  
Drug Administration ◽  
Breath Test ◽  
Dihydropyrimidine Dehydrogenase ◽  
Metabolite Formation ◽  
Colorectal Cancer Patients ◽  
Further Development

2551 Background: The UraBT is currently in development as a phenotypic test to screen for DPD deficiency. Following an oral dose of 2-13C-uracil, the UraBT shows a significant relationship between breath 13CO2 metabolite formation and plasma 2-13C-uracil and 2-13C-dihydrouracil pharmacokinetics. We herein describe a novel, potentially more clinically relevant test in which a small oral dose of 2-13C-5-fluorouracil (5-FU) is administered, followed by assessment of breath 13CO2 metabolite formation as previously described for the UraBT. We hypothesize that the FUBT can rapidly assess interindividual variability in 5-FU catabolism and predisposition to 5-FU toxicity. Methods: Over two sessions separated by a seven day washout, a single dose (6mg/kg, p.o.) of 2-13C-uracil or 2-13C-5-FU was administered to patients with stage III-IV colorectal cancer (n = 4). Subsequent to drug administration, in each session, 13CO2 catabolite formation was quantified in the breath over eight hours. In a separate investigation over two sessions separated by a seven day washout, a single dose (3mg/kg, p.o.) of 2-13C-uracil or 213C-5-FU was administered to colorectal cancer patients with previously documented severe (n=2) or moderate (n=2) 5-FU dose-related hematological/gastrointestinal toxicity. Following drug administration 13CO2 catabolite formation was quantified over eight hours. 13CO2 concentration was expressed as Delta Over Baseline (DOB) in all sessions. Results: Compared to the UraBT, the FUBT showed an increased Cmax (50.7 ± 6.6 DOB/mg vs. 36.8 ± 7.8 DOB/mg; mean ± SD) and decreased Tmax (25 ± 4 min vs. 45 ± 6 min) for 13CO2 formation (p<0.05). The FUBT was able to distinguish patients with previously reported severe and moderate 5- FU toxicity, with 13CO2 Cmax values of 35.5 ± 9.5 DOB/mg (mean ± SD) and 59.8 ± 7.3 DOB/mg, respectively. Importantly, FUBT Cmax values positively correlated with DPD activity (rs=1.00, p<0.01). Conclusions: These data lend support to further development of the FUBT as a rapid and informative test to assess DPD activity and to predict susceptibility to severe dose-related 5-FU toxicity. [CA116964] No significant financial relationships to disclose.

scholarly journals Potential of Dihydropyrimidine Dehydrogenase Genotypes in Personalizing 5-Fluorouracil Therapy Among Colorectal Cancer Patients

2013 ◽  
pp. 1 ◽  
Author(s):  
Lay Kek Teh ◽  
Sharina Hamzah ◽  
Hazwanie Hashim ◽  
Zakaria Bannur ◽  
Zainul Amiruddin Zakaria ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dihydropyrimidine Dehydrogenase ◽  
Colorectal Cancer Patients
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