5-6-7-8-tetrahydrofolic-acid and Stomach-Neoplasms

The purpose of the current study is to evaluate the efficacy and complications of concurrent chemoradiotherapy (CCRT) for the treatment of gastric cancer patients after D1/D2 surgery.. Sixty-eight untreated gastric cancer patients (T3/T4 and/or N+) were enrolled. After surgery, they were randomized into two groups: the CCRT group and the single chemotherapy group. Radiotherapy patients were treated according to the Intergroup 0116 guidelines. The chemotherapy consisted of continuously administered 5-fluorouracil (5-FU) and tetrahydrofolic acid (LV). The CCRT began 28 days after the first cycle of chemotherapy, and chemotherapy was given within the first four and last three days during the CCRT period, at a radiation dosage of 45 Gy/25 f, i.e., 1.8 Gy 5 times per week. Two cycles of the same chemotherapy were administrated 1 month after the radiotherapy. Five cycles of 5-FU and LV were applied to CG.. One-, two-, and three-year survival rates were 85.9, 73.4, and 67.7%, respectively, in the CCRT group and 68.0, 50.0, and 44.1%, in the single chemotherapy group (P < 0.05). The corresponding disease-free survival rates were 73.5, 64.7, and 55.8% in the CCRT group and 61.8, 38.2, and 29.4% in the single chemotherapy group (P < 0.05). The major side effects were gastrointestinal reactions and neutrocytopenia. In both the CCRT and single chemotherapy groups, the incidence of these side effects was 73.5% (25/34) and 44.1% (15/34) (P < 0.05) for Grade I and Grade II anorexia, 82.35% (28/34) and 73.5% (25/34) (P > 0.05) for nausea and vomiting, and 70.6% (24/34) and 44.1% (15/34) (P < 0.05) for neutrocytopenia, respectively. The other indices showed no significant differences.. Our findings indicate that CCRT can increase the one-, two-, and three-year total survival rates, as well as the disease-free survival rates of gastric cancer patients (T3/T4 and/or N+) who have been initially treated with surgery. The major adverse reactions were Grade I and Grade II nausea and vomiting, as well as myelosuppression. CCRT is well tolerated.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Radiotherapy, Adjuvant; Radiotherapy, Intensity-Modulated; Stomach Neoplasms; Survival Rate; Tetrahydrofolates

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drugs, Chinese Herbal; Female; Fluorouracil; Humans; Male; Middle Aged; Phytotherapy; Stomach Neoplasms; Tetrahydrofolates

Currently, biochemical modulation for 5-fluorouracil (5-FU) is one of the most successful chemotherapy for both colo-rectal and gastric cancer. The purpose of this study is to evaluate the significance of measuring intratumoral thymidylate synthetase (TS) and folate (FH4) levels as predictive parameters for the successful treatment. Samples were collected from 16 advanced colo-rectal and 21 advanced gastric cancer. TS and tetrahydrofolate levels in the specimens were measured by binding assay. Results showed that there were no significant difference in TS levels between the different pathologic types of carcinoma. On the other hand, well (3.94 +/- 1.75 p mol/g) and moderately (5.95 +/- 2.69 p mol/g) differentiated carcinoma showed lower FH4 levels compared to poorly differentiated carcinoma (9.58 +/- 5.27 p mol/g). In conclusion, biochemical modulation by cisplatin or leucovorin, which elevates intratumoral folate levels, is more needed for well and moderately differentiated carcinoma. Finally, measuring TS levels can also be important because two cases who responded to cisplatin/5-FU chemotherapy showed low TS levels compared to the others who had lower response.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Fluorouracil; Humans; Stomach Neoplasms; Tetrahydrofolates; Thymidylate Synthase

Various factors, including thymidylate synthase, thymidine kinase, 5-fluorouracil phosphorylation and degradation pathways, folate concentrations, and the stability of ternary complex, which influence thymidylate synthase inhibition rate of fluoropyrimidines, were studied in 87 human adenocarcinoma tissues.. The activity of the 5-fluorouracil degradation pathway was not significantly lower than the activity of the 5-fluorouracil phosphorylation pathway. The activity of the catabolism pathway of 5-fluorouracil should be considered in human adenocarcinoma tissue during chemotherapy. On the other hand, the means plus or minus standard deviations (means +/- SD) of the concentration of 5,10-methylenetetrahydrofolate and tetrahydrofolate were 0.69 +/- 0.54 and 1.25 +/- 0.69 nM, respectively, for the adenocarcinoma tissues without previous chemotherapy.. Because the half-life of tritium-labeled ternary complex and folate concentration in cytosol were correlated well, the differences in folate concentration among tumors must influence the dynamic equilibrium of ternary complex formation. Moreover, these results show that the ratio of 5,10-methylenetetrahydrofolate concentration to thymidylate synthase concentration influences the thymidylate synthase inhibition rate in tumor, and that the new synthesis of 5,10-methylenetetrahydrofolate and tetrahydrofolate from other endogenous reduced folates is also important in tumors with high thymidylate synthase concentrations.

Topics: Adenocarcinoma; Colorectal Neoplasms; Culture Techniques; Fluorouracil; Folic Acid; Humans; Leucovorin; Lymph Nodes; Phosphorylation; Stomach Neoplasms; Tetrahydrofolates; Thymidine Kinase; Thymidylate Synthase