Relationships Between Dihydropyrimidine Dehydrogenase Activity In Blood And The Response And Adverse Events Of Chemotherapy In Esophageal Cancer

Objective: To investigate the correlation of dihydropyrimidine dehydrogenase(DPD) activity in blood with the response and adverse events of chemotherapy in esophageal cancer. And to explore the feasibility that clinical T, N stage was applied to response evaluation of the neo-adjuvant and palliative chemotherapy.Methods: Dihydrouracil and uracil(H2U/U) ratio in serum which represents indirectly DPD activity in blood were assayed by high performance liquid chromatography(HPLC) before chemotherapy. The chemotherapy protocol was FLP that consisted of leucovorin (100mg/m2) ,5-fluorouracil (500mg/m2) and cisplatin (15mg/m2 ) from day 1 to day 5, 4 weeks as a cycle. Adverse events of the chemotherapy were scored according to CTCAE3.0 for the whole patients. The TNM staging in the patients who received neo-adjuvant or palliative chemotherapy confirmed by barium meal X-ray film and CT scans. And the responses were evaluated according to RECIST after 2 cycles chemotherapy.Results: 133 cases of patients with chemotherapy indication were enrolled in the study, in which the group of neo-adjuvant chemotherapy was 68 cases that included T1 2 cases, T2 31 cases, T3 24 cases and T4 11 cases, and corresponded clinical stage wereⅢphrase 45 cases andⅣphrase 23 cases, the group of adjuvant chemotherapy 41 cases, and the group of palliative chemotherapy 24 cases. The DPD activity in blood was expressed in normal distribution (ranged 0.69 to 6.79). The mean and median value were 2.68 and 2.73 respectively, and standard deviation was 0.99(95%CI2.44～2.94). The DPD activities were much variable among patients, but none of them were thorough deficient. The DPD activity had no correlation with sex, age, education degree, and also site, X-rays type, histology type, staging of the tumor, operation history, radiotherapy history and KPS (P>0.05). The toxicities of chemotherapy were slight, and no case was discontinued chemotherapy because of severe adverse events. Spearman analysis demonstrated that DPD activity correlated with chemotherapy toxicities including nausea, vomiting, myelosuppression, diarrhea, oral mucositis, fatigue, et al(P<0.05). Therapy response could be evaluated in 89 cases, in which CR 1 case, PR 39 cases, SD 36 cases, and PD 13 cases. The RR was 45%. The mean value of the DPD activity was lower in the group of chenotherapy-responsive patients than in the group of ineffective patients (2.38 and 3.29 respectively), but had no statistical significance between the groups(t=5.923, P>0.05).Conclusions: FLP regimen was safe and effective to esophageal cancer. DPD activity in blood were negatively correlated with 5-FU toxicities, while had no correlation with the chemotherapy response and clinical pathological parameters. Clinical T and N stage evaluation according to barium meal X-ray film and CT scans are consistent with RECIST and more convenient for the judgement of response in neo-adjuvant and palliative chemotherapy of esophageal cancer.