1.
Effects of 5-fluorouracil on oxidative stress and calcium levels in the blood of patients with newly diagnosed colorectal cancer.
Koçer, M, Nazıroğlu, M
Biological trace element research. 2013;(3):327-32
Abstract
The administration of chemotherapeutic agents for colorectal carcinoma is associated with an increase in oxidative stress and a concomitant decrease in antioxidant and element levels in the blood. This study investigated the effects of 5-fluorouracil (5-FU) chemotherapy on the levels of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), antioxidant vitamins, and elements in colorectal cancer patients. Twelve patients with newly diagnosed colorectal carcinoma and 12 healthy subjects were included in this study. Blood samples were collected from both the healthy controls and patients. 5-FU was intravenously administered to the patients for 6 weeks, and blood samples were collected again from the treatment group. In the patient group, lipid peroxidation levels were increased in both the plasma and erythrocyte samples, whereas GSH-Px activity and concentrations of GSH, vitamin E, and β-carotene in erythrocytes were decreased. The oxidant, antioxidant, and plasma calcium values were lower in 5-FU-treated patients than in the controls. Plasma vitamin A, chloride, sodium, and potassium concentrations did not change with 5-FU treatment. In conclusion, oxidative stress in patients with newly diagnosed colorectal cancer is attributable to the disease and not to 5-FU treatment. Blood vitamin E, β-carotene, GSH, and GSH-Px levels could be useful as early biomarkers of the prognosis of colorectal cancer patients.
2.
Preoperative radio-chemotherapy (RT-CT) in rectal cancer. Prospective study with postoperative RT-CT control group.
Cambray i Amenós, M, Navarro García, M, Martí Ragué, J, Pareja Fernández, L, Pera Fábregas, J
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2007;(3):183-91
Abstract
INTRODUCTION Between 1996 and 2000, the colorectal tumour committee of the Hospital Universitario de Bellvitge and the Institut Català d'Oncologia, Hospitalet, carried out a non-randomised prospective study of pre-op radio-chemotherapy (RT-CT) in locally advanced rectal tumours. We herein present the results. On the other hand, and at the same time, patients operated on for locally advanced rectal cancer were admitted and treated by RT-CT during the postoperative process, according to our standard protocol. Results for both series are compared. MATERIAL AND METHODS The preoperative RT-CT group included 94 patients. They received radiotherapy (RT), 45 Gy on posterior pelvis, and simultaneously, 5-fluorouracil (5FU) by continuous infusion (300 mg/m2/day, 5 days weekly during RT). Surgical intervention was scheduled 6-8 weeks after preoperative treatment; after surgery they received 5FU (425 mg/m2/day) and leucovorin (20 mg/m2/day) bolus, 5 days weekly; 4 cycles at four-week intervals. 237 patients who had been previously operated on and who had been staged as T3-T4 and/or N+, M0 were admitted to our centre during the same time period and received postoperative RT-CT. RESULTS The preoperative treatment group showed a complete and global response rate to RT-CT in 17% and 68% of cases, respectively. Anal sphincter was preserved in 38.5% of patients exhibiting low rectal tumours (inferior limit of tumour at 6 cm or less from the anal margin). Overall and disease-free survival at 5 years was distinct, showing statistical significance, according to the response obtained through preop treatment; it was better in responsive patients (overall survival: 87% in complete remissions, 75% in partial remissions, 48% in stable disease, and mean survival was 0.84 years for patients who evolved, p<0.05; disease-free survival was: 93% in complete remission, 76% partial remission, 39% in stable disease, p=0.001). We did not see any difference with regard to overall survival, disease-free survival or local control at the time of comparing either pre- or postoperative groups. There were, however, differences with regard to late toxicity; they showed less toxicity when RT-CT was administered preoperatively; no case of radiation enteritis that required surgery was seen in this group, whereas in the postoperative RT-CT it was 4.2%, p=0.022. CONCLUSIONS Preoperative treatment of locally advanced rectal cancer is recommended, for it yields a high level of response to treatment; it allows preservation surgery of the anal sphincter in one third of patients showing low rectal tumours. There is also a clear diminution of late toxicity with pre-op treatment. On the other hand, response to pre-op treatment selects patients with a better prognosis.
3.
The effect of food on the pharmacokinetics of S-1 after single oral administration to patients with solid tumors.
Peters, GJ, Noordhuis, P, Van Groeningen, CJ, Giaccone, G, Holwerda, U, Voorn, D, Schrijvers, A, Schornagel, JH, Beijnen, JH, Fumoleau, P, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004;(12 Pt 1):4072-6
Abstract
PURPOSE The purpose is to determine the effect of food on the bioavailability of S-1, an oral formulation of the 5-fluorouracil (5FU) prodrug Ftorafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), a dihydropyrimidine dehydrogenase inhibitor, and oxonic acid (an inhibitor of 5FU phosphoribosylation in normal gut mucosa) in a molar ratio of 1:0.4:1. EXPERIMENTAL DESIGN Eighteen patients received a single dose of S-1 of 35 mg/m(2) with (535-885 kcal) or without food in a crossover study design: in arm A without breakfast on day -7 and with breakfast on day 0 and in arm B the reversed sequence. Blood samples were taken before and after S-1 administration. This food effect was evaluated according to the Food and Drug Administration guidelines using log-transformed data. RESULTS Pharmacokinetic parameters for 5FU without breakfast were as follows: Tmax, 107 min; Cmax, 1.60 microm; area under the plasma concentration-time curve (AUC) 441 microm x min; and T(1/2), 104 min. Fasting decreased Tmax of FT, 5FU, CDHP, and oxonic acid significantly (P < 0.006) and increased the Cmax (P < 0.013). The food/fast ratio for the AUC of FT was not different, which for 5FU was 0.84 (P = 0.041), for CDHP was 0.89 (P = 0.191), for oxonic acid was 0.48 (P < 0.0005), and for cyanuric acid, the breakdown product of oxonic acid, was 5.1 (P = 0.019). Accumulation of uracil, indicative for dihydropyrimidine dehydrogenase inhibition, was not affected, as well as the T(1/2) of FT, 5FU, CDHP, and oxonic acid. Evaluation of the log-transformed data demonstrated that the 90% confidence interval for the food/fast ratio for the Cmax and AUC of FT, 5FU, CDHP, and uracil were within 70-143% and 80-125%, respectively, indicating no food effect. Only for oxonic acid and cyanuric acid were these values outside this interval. CONCLUSIONS Food intake affected only the pharmacokinetics of the S-1 constituent oxonic acid but not of FT, CDHP, and 5FU. Because oxonic acid is included to protect against gastrointestinal toxicity, this observation might affect the gastrointestinal toxicity and thus the efficacy of S-1.
4.
Comparison of a 48-hour infusion of 5-fluorouracil without folinic acid with 24-hour folinic acid/5-fluorouracil in patients with metastatic colorectal cancer refractory to bolus folinic acid/5-fluorouracil. A prospective cohort study.
Moehler, M, Gutzler, F, Steinmann, S, Boehme, M, Raeth, U, Stremmel, W, Galle, PR, Rudi, J
Chemotherapy. 2003;(1-2):85-9
Abstract
BACKGROUND Out of various high-dose 5-fluorouracil (5-FU) regimens given with or without folinic acid (FA), the optimal 5-FU schedule has still to be defined as treatment for metastatic colorectal cancer (CRC). Consequently, we compared toxicity, response and survival following two FA/5-FU regimens in 55 CRC patients refractory to bolus FA/5-FU. METHODS Twenty-eight patients (group A) received 5-FU (60 mg/kg body weight) for 48 h, and 27 (group B) received 2-hour infusions of FA (500 mg/m(2)) and 24-hour infusions of 5-FU (2600 mg/m(2)) until disease progression. RESULTS Both groups were adequately matched with respect to patient characteristics. While overall toxicities were rare, hand-foot syndrome was more common in A. Tumor control was achieved in 57 and 44%, for A and B, respectively. Survival times were 16 months in A and 9 months in B. CONCLUSIONS Since both 5-FU infusion protocols showed equivalent palliative effects, FA may be questioned in second-line 5-FU regimens.