This study revealed that DPYD*5 (rs1801159) and 1896 T>C (rs17376848) are potentially useful predictive markers of patients' responses to 5-FU chemotherapy. Pharmacogenotyping is therefore recommended to guide dosing of 5-FU and prevent neutropenia.

Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.

Aim:To evaluate two cases of gemcitabine-induced radiation recall in patients who were treated for localized pancreatic cancer, and review the literature. Methods: The two cases of radiation recall (from a cohort of 80 patients treated for pancreatic carcinoma) were retrospectively identified using patient medical records. Prior publications were identified through an English language literature search of MEDLINE Ovid from January 1966 to October 2006, using the key words gemcitabine and radiation recall. Results: Both the radiation recall reactions were limited to the gastrointestinal system, localized to previous radiotherapy field. No pathology was identified on radiological investigation. The onset of the radiation recall phenomenon was 2 and 10 days, respectively, from the time gemcitabine was initiated. The treatment of radiation recall consisted of the cessation of gemcitabine, initiating steroid therapy and supportive therapy. Both of the patients' symptoms achieved complete resolution. A comprehensive review of the literature found 15 previous cases of radiation recall related to gemcitabine but one reported effect involving the gastrointestinal system. Previously reported sites of recall phenomena included the skin, muscles, brain stem and optic nerve. In the treatment of pancreatic carcinomas, there were only four reported cases, three involving the onset of myositis of abdominal muscle and one case of gastrointestinal bleeding. Conclusion: Radiation recall from gemcitabine chemotherapy is uncommon. It can potentially arise in any site that has been irradiated previously. The treating doctor needs to be aware of this phenomenon to be able to manage this condition appropriately.