Prognostication of pancreatic adenocarcinoma by expression of thymidine phosphorylase/dihydropyrimidine dehydrogenase ratio and its correlation with survival.
Expert Opin Drug Saf
; 8(5): 507-14, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19663627
ABSTRACT
BACKGROUND:
Dihydropyrimidine dehydrogenase (DPD) is the first rate limiting enzyme that catabolizes 5-fluorouracil. Thymidine phosphorylase (TP) catalyzes the last step that converts capecitabine into 5-fluorouracil. The TP/DPD ratio has suggested a positive correlation with the efficacy of capecitabine in human xenograft models. This is the first human study that analyzes the association of TP/DPD ratio with overall survival and disease-free survival in cases of locally advanced pancreatic cancer (LAPC).METHODS:
A total of 35 patients with newly diagnosed LAPC received 50.4 Gy radiotherapy with capecitabine 1,600 mg/m(2) followed by capecitabine 2,000 mg/m(2) x 14 days every 3 weeks till progression. Tumor specimens were procured with endoscopic ultrasound-guided fine-needle aspiration before and after week 2 of starting capecitabine radiotherapy to evaluate TP and DPD mRNA levels by reverse transcription polymerase chain reaction (RT-PCR).RESULTS:
The paired t-tests showed no relationship between mRNA TP or DPD levels or TP/DPD ratio and disease-free survival. The log-rank test revealed that the lower TP/DPD ratio was statistically significantly associated with a higher overall survival with an average of 304 days in the lower TP/DPD ratio group and 172 days in the higher TP/DPD group (a difference of 132 days).CONCLUSIONS:
We found a survival benefit of approximately 4 months in our study correlating with lower TP/DPD ratio and this is quite significant in a disease whose > 5-year survival is < 5%. The TP/DPD ratio may be used as an independent marker for prognostication for LAPC and it may help in determining the chemotherapy duration, choices and possibly toxicities as well. Larger studies are needed to study the relation ship between TP/DPD ratio with these efficacy parameters.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Timidina Fosforilase
/
Adenocarcinoma
/
Di-Hidrouracila Desidrogenase (NADP)
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Expert Opin Drug Saf
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos