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At least 109 records · Page 6Linked to original sources
PubMed2005

Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC.

Two i.v. regimens, bendamustine, methotrexate and 5-fluorouracil (BMF) and cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were compared as first-line therapy in a randomized, open, multicenter phase III trial including 364 patients with metastatic breast cancer (MBC). Bendamustine is an anti-neoplastic agent with alkylating, but also additional, so far unclear, mechanisms of action. We wanted to show the superiority of BMF over CMF in terms of time to progression (TTP) (primary endpoint), overall response, response duration, toxicity and quality of life (QoL). TTP was significantly longer in the BMF group (8.2 versus 6.7 months for CMF) (p=0.0071). The effect of BMF on TTP was more pronounced in the stratum 'prior adjuvant therapy, no visceral metastases' (p=0.034). Overall response rates and QoL did not significantly differ between the regimens. BMF caused more mucositis and leukopenias. Thus, bendamustine, when replacing cyclophosphamide in the CMF combination, can be expected to produce longer progression-free survival in first-line treatment of MBC.

Adolescent↗
PubMed2004

Intensified bimonthly cisplatin with bolus 5-fluorouracil, continuous 5-fluorouracil and high-dose leucovorin (LV5FU2) in Patients with advanced gastrointestinal carcinomas: a phase I dose-finding and pharmacokinetic study.

5-fluorouracil (5FU) and cisplatin are commonly used in the treatment of gastric cancer. Continuous 5FU appears to be more effective and less toxic than bolus administration, while increasing the dose intensity of cisplatin may be advantageous. We conducted a phase I study to establish the maximum tolerated dose (MTD) of cisplatin, which could be combined with a hybrid bolus/continuous 5-FU regimen (LV5FU2), given every 2 weeks. Thirty-six patients with advanced upper gastrointestinal carcinomas entered the study. Starting cisplatin dose was 40 mg/m2 and it was increased by 10 mg/m2 in cohorts of 3-6 patients. The pharmacokinetics of 5-fluorouracil in 14 patients were compared with those of 6 patients receiving LV5FU2 alone. All patients received prophylactic granulocyte colony-stimulating factor at cisplatin doses > or =50 mg/m2. MTD was reached at 100 mg/m2 of cisplatin and, therefore, the 90 mg/m2 dose is recommended for phase II studies. Bone marrow toxicity was the most frequent dose-limiting toxicity with 1 patient dying of neutropenic sepsis. Grade III/IV neutropenia was observed in 10 patients (27.7%). Nonhematological toxicity was infrequent and mild. Pharmacokinetic analysis showed that the addition of 90 mg/m2 or 100 mg/m2 of cisplatin to LV5FU2 significantly reduced the 5FU area under the curve. Objective response rate in 23 evaluable patients was 39.2%. The combination of LV5FU2 with bimonthly 90 mg/m2 cisplatin is feasible and active and should be further evaluated in patients with advanced gastric cancer.

Adult↗
PubMed2000

A novel class of antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), that releases 5-fluorouracil upon hypoxic irradiation.

We have been developing prodrugs of anticancer agents such as 5-fluorouracil (5-FU) that are activated by irradiation under hypoxic conditions via one-electron reduction. Among them, OFU001 [1-(2'-oxopropyl)-5-fluorouracil] is a prototype radiation-activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5-FU through incorporation of hydrated electrons into the antibonding sigma * orbital of the C(1')-N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O(2) into superoxide anion radicals (O(2).(-)) under conditions of aerobic irradiation. Therefore, 5-FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5-FU with a G-value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9 x 10(-7) mol / J following hypoxic irradiation, while the G-value for 5-FU release was 1.0 x 10(-8) mol/J following aerobic irradiation. However, the G-values for decomposition of OFU001 were almost the same, i.e., 3.4 x 10(-7) mol/J following hypoxic irradiation and 2. 5 x 10(-7) mol / J following aerobic irradiation. When hypoxically irradiated (7.5 - 30 Gy) OFU001 was added to murine SCCVII cells for 1 - 24 h, a significant cell-killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5-FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents.

Animals↗
PubMed2004

Phase II study of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil (MVPF) in patients with metastatic large bowel cancer: an Eastern Cooperative Oncology Group study (EST 1285).

PURPOSE: To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil (MVPF) in patients with metastatic large bowel cancer. PATIENTS AND METHODS: A total of 94 patients with no prior chemotherapy and measurable metastatic large bowel cancer were randomly assigned to one of the two treatment regimens. Eastern Cooperative Oncology Group (ECOG) criteria were used to evaluate response and toxicity. RESULTS: Fifty patients were randomized to PF and 44 to MVPF. Toxicity was evaluable in all patients except one; response was evaluable in 40 and 31, with response rate of 13 and 42%, respectively. Intent-to-treat analysis showed a response rate of 12 and 32%, respectively (p = 0.076), where it was assumed that none of the ineligible or unevaluable patients responded. Median survival for all patients was 9 months, with no difference between PF and MVPF. ECOG Performance Status (0 vs. 1), weight loss (< or =10 vs. >10%) and site of metastatic lesion had statistically significant impact on survival. MVPF was definitely more toxic than PF (p < 0.000005). CONCLUSION: Both treatment regimens showed clinical activity. The MVPF regimen resulted in more responses than PF, no improvement in survival, and more toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

5-Fluorouracil, adriamycin, cyclophosphamide (FAC) vs. 5-fluorouracil, epirubicin, cyclophosphamide (FEC) in metastatic breast cancer.

94 evaluable patients with metastatic breast cancer were randomly assigned to 5-fluorouracil, adriamycin, and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), with cycles repeated every 3 weeks. The objective response rate to FAC was 46% versus 44% to FEC. There was no significant difference in the median duration of response and median survival for the two regimens. Toxicity was more frequent and more pronounced in patients receiving FAC. Results indicate therapeutic equivalence of the two regimens and reduced toxicity of the epirubicin arm.

Adult↗
PubMedDate not supplied

Comparison of 5-fluorouracil, doxorubicin and mitomycin C with 5-fluorouracil alone in the treatment of pancreatic-biliary carcinomas.

In this multicenter randomized trial, the efficacy of combination chemotherapy using 5-fluorouracil, doxorubicin and mitomycin C (arm A) was compared with that of 5-fluorouracil alone (arm B) in 81 patients with nonresectable carcinomas of the pancreas or biliary tract. There were no significant differences between treatment arms regarding the median time to progressive disease, median survival time, palliative effects or toxicities. It was concluded that combination chemotherapy is feasible but cannot be recommended.

Adult↗
PubMed1995

Chemotherapy in gastric cancer: an economic evaluation of the FAM (5-fluorouracil, adriamycin, mitomycin C) versus ELF (etoposide, leucovorin, 5-fluorouracil) regimens.

The prognosis in gastric cancer has been almost unchanged for the last 20 years. At the time of diagnosis the majority of patients have disseminated disease. The 5-year survival is only about 15%. Several efforts with numerous antineoplastic regimens have been studied. The most widely used regimen has been the FAM (5-fluorouracil, adriamycin, mitomycin C) regimen. Because of the cardiotoxicity and dose intensity of the FAM regimen, a low toxicity regimen, the ELF (etoposide, leucovorin, 5-fluorouracil) regimen, has been introduced. We present the data from the treatment of 26 patients (17 FAM, 9 ELF) with advanced gastric cancer at the University Hospital of Tromsø. The monthly costs of FAM and ELF treatment were calculated to a price of 553 pounds and 2976 pounds (British pounds). The median survival of 5 months (FAM) and 6 months (ELF) is in accordance with other studies. Assuming that the median survival in our study is correct, the cost of one year saved was 123,834 pounds, while the cost of one QALY (quality adjusted life year) employing the ELF compared to the FAM regimen was 104,334 pounds. We conclude that the standard ELF regimen too expensive in the treatment of gastric cancer.

Adult↗
PubMed1996

Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group.

PURPOSE: To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in premenopausal women with axillary node-positive operable breast cancer. PATIENTS AND METHODS: The International Collaborative Cancer Group (ICCG) conducted a large randomized trial in which two alternative schedules were used according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2. RESULTS: Seven hundred fifty-nine patients were entered onto the trial. At a median follow-up time of 4.5 years, no significant benefit for the anthracycline-containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2 had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea and vomiting and alopecia were more common in the epirubicin-containing regimen (P = .001). CONCLUSION: We conclude that the FEC2 regimen, in which epirubicin replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen for premenopausal patients with operable axillary node-positive breast cancer.

Adult↗
PubMed1996

Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration.

PURPOSE: To determine the long-term impact on disease-free survival (DFS) and overall survival (OS) of adjuvant anthracycline-based chemotherapy, when prospectively compared by random allocation with standard cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive (N+) breast cancer patients. PATIENTS AND METHODS: Two hundred forty-nine patients with N+ breast cancer, recruited from eight French cancer centers, were randomized to receive 12 monthly cycles of adjuvant chemotherapy, either CMF (n = 112) or doxorubicin, vincristine, cyclophosphamide, and fluorouracil (AVCF) (n = 136). All had a negative metastatic work-up before inclusion, which was stratified by accrual center, tumor stage (International Union Against Cancer [UICC]), and menopausal status. RESULTS: No severe adverse effect related to grade 4 (World Health Organization [WHO]) toxicity was observed. There was no difference in second primary tumor incidence between the two arms. The treatment given was 88% of planned for AVCF and 75% for CMF in both premenopausal and menopausal patients. With a median follow-up time of 16 years (range, 13 to 17), the OS and DFS rates are significantly longer in the AVCF arm (56% v 41% [P = .01] for OS, and 53% v 36% [P = .006] for DFS). These differences are significant, irrespective of tumor stage (T1 to T2 v T3 to T4), and remain positive in patients with or without postoperative locoregional radiotherapy (55% of cohort). When analyzed according to menopausal status, the differences remain significant only for premenopausal patients. CONCLUSION: This set of mature controlled data confirms the added value of anthracycline-based combination adjuvant therapy for N+ breast cancer patients when compared with CMF, with both regimens given for 1 year.

Adult↗
PubMed1996

Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil.

PURPOSE AND METHODS: We identified patients with gastric cancer at high risk for recurrence before therapy using endoscopic ultrasonography (EUS). Neoadjuvant therapy using the fluorouracil, doxorubicin, and metrotrexate (FAMTX) regimen was given for three courses before planned laparotomy with the intention to perform curative resection. Postoperatively, intraperitoneal (IP) cisplatin and fluorouracil (FU) and intravenous (i.v.) FU were administered to patients undergoing resection. RESULTS: Fifty-six assessable patients were treated. Preoperative FAMTX therapy was tolerable, with the major toxicity being neutropenic fever. One treatment-related death was seen. Eighty-nine percent of patients underwent surgical exploration and 61% had potentially curative resections. There were two postoperative deaths. Comparison of pathologic tumor (pT) stage with EUS-predicted tumor stage showed apparent downstaging in 51% of patients. Postoperative IP chemotherapy was delivered to 75% of eligible patients. Toxicity was acceptable. There was no increase in operative morbidity or mortality compared with concurrent nonstudy patients undergoing a similar operative procedure and not receiving preoperative therapy. With a median follow-up time of 29 months, the median survival duration was 15.3 months. For patients who underwent potentially curative resections, the median survival duration was 31 months. Peritoneal failure was seen in 16% of patients. CONCLUSION: Chemotherapy with the FAMTX regimen is tolerable in patients with locally advanced gastric cancer, without an increase in operative morbidity or mortality. IP therapy can be successfully delivered to most resected patients. The intraabdominal failure pattern appears to be decreased compared with expected. This approach is an appropriate investigational arm to pursue in future studies.

Adenocarcinoma↗
PubMed2004

Four decades of continuing innovation with fluorouracil: current and future approaches to fluorouracil chemoradiation therapy.

PURPOSE: Chemoradiotherapy, the combination of external radiation therapy and concurrent chemotherapy, has been the basis for the oncologic management of many patients since its development in the 1960s. Fluorouracil (FU) chemoradiotherapy has demonstrated success in several organ sites with multiple dosing schedules that now guide the selection of oral analogs of FU to provide new chemoradiotherapy options. METHODS: This article reviews the metabolism and pharmacology of FU and the advantages of administration of FU by continuous infusion or bolus. The potential role and impact of the oral fluorouracil prodrugs UFT, S-1, BOF-A2, and capecitabine as replacements for intravenous administration are discussed. The results of recent chemoradiotherapy studies with FU from 2000 to 2003 are summarized in rectal, head and neck, esophageal, gastric, pancreatic, biliary, anal, and cervical cancers. RESULTS: Chemoradiotherapy with FU has the potential to widen the therapeutic window by minimizing normal tissue toxicity while maintaining effective tumor toxicity. Overall, FU chemoradiotherapy maximizes local control and, for some tumor sites (such as head and neck, pancreatic, biliary, cervical, esophageal, and gastric cancers), improves survival rates. Moreover, FU chemoradiotherapy results in improved organ preservation with excellent functional outcome in several anatomic sites including head and neck cancer, anal, and rectal cancer, with improved sphincter preservation. CONCLUSION: FU chemoradiotherapy continues to play an important role in the management of many cancer sites. During the last four decades, optimal dosing schedules have produced a therapeutic gain. The introduction of oral prodrug analogs will likely further improve the results of FU therapy in several organ systems, such as the rectum, head and neck, and esophagus.

Antimetabolites, Antineoplastic↗
PubMed2005

Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281.

PURPOSE: Optimal treatments for metastatic carcinoid tumor remain undefined, and the role of chemotherapy for symptomatic patients with progressive disease is uncertain. PATIENTS AND METHODS: Two hundred forty-nine patients with advanced carcinoid tumors were randomized to either doxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ). Patients crossed over to the dacarbazine (DTIC) treatment after disease progression following first-line treatment (either FU/DOX or FU/STZ), and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function. RESULTS: In the randomized group, there was no difference between FU/DOX and FU/STZ in response rates (15.9% v 16%) and progression-free survival (4.5 v 5.3 months). FU/STZ (24.3 months) was superior to FU/DOX (15.7 months; P = .0267) in median survival. The response rate of crossover DTIC treatment was 8.2%, with a median survival of 11.9 months. Hematologic toxicities were the major treatment-related toxicities for both FU/DOX and FU/STZ, and mild to moderate renal toxicity was reported in 40 (34.8%) of 115 patients in the FU/STZ arm. CONCLUSION: Response to all three treatment regimens were modest. FU/STZ improved survival compared with the doxorubicin-based regimen, suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors.

Adult↗
PubMed2005

Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102.

PURPOSE: We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status. PATIENTS AND METHODS: Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided P values for planned comparisons were calculated. RESULTS: Ten-year estimates indicated that CAF was not significantly better than CMF (P = .13) for the primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to 1.43); values were statistically significant in the planned one-sided test (P = .03). Toxicity was greater with CAF and did not increase with TAM. Overall, TAM had no benefit (DFS, P = .16; OS, P = .37), but the TAM effect differed by HR groups. For HR-positive patients, TAM was beneficial (DFS, HR = 1.32 for no TAM v TAM; 95% CI, 1.09 to 1.61; P = .003; OS, HR = 1.26; 95% CI, 0.99 to 1.61; P = .03), but not for HR-negative patients (DFS, HR = 0.81 for no TAM v TAM; 95% CI, 0.64 to 1.03; OS, HR = 0.79; 95% CI, 0.60 to 1.05). CONCLUSION: CAF did not improve DFS compared with CMF; there was a slight effect on OS. Given greater toxicity, we cannot conclude CAF to be superior to CMF. TAM is effective in HR-positive disease, but not in HR-negative disease.

Adolescent↗
PubMed2005

retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group.

PURPOSE: The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. PATIENTS AND METHODS: In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. RESULTS: HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). CONCLUSION: TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.

Antigens, Neoplasm↗
PubMed2001

Plasma, intestine and tumor levels of 5-fluorouracil in mice bearing L1210 ascites tumor following oral administration of 5-fluorouracil, UFT (mixed compound of tegafur and uracil), carmofur and 5'-deoxy-5-fluorouridine.

Several 5-fluorouracil (5-FU) derivatives, 1-hexylcarbamoyl-5-fluorouracil (HCFU), 5'-deoxy-5-fluorouridine (5'-DFUR) and UFT (mixed compound of tegafur and uracil), have been developed and clinically widely used. However, comparative pharmacokinetic studies of the parent compound and other fluorinated drivatives have not been precisely reported. The dosage of the oral clinical use for human cancer of 5-FU, HCFU, 5'-DFUR and UFT as tegafur (FT) is 200-300mg/d, 600mg/d, 800-1,200mg/d and 300-600mg/d respectively. These amounts of the drugs are almost equimolar. Previously, we reported the effect of oral equimolar administration of each four drugs on thymidilate synthase activity, deoxyribonucleotide metabolism and cell cycle progression in L1210 ascites tumor. (1,2) In this study, we examined the antitumor effect and 5-FU concentration in the plasma, intestine and tumor after oral equimolar administrations of each drug using BDF1 mice bearing L1210 ascites tumor. In our study, UFT showed the best life prolongation among these four drugs. The intestine 5-FU level was highest by treatment with 5-FU during the initial 4 h. The plasma 5-FU level was highest by treatment with HCFU for 4 h. But the tumor 5-FU level was highest by treatment with UFT over the 24 h. In spite of the high plasma 5-FU concentration after the treatment with HCFU, the 5-FU concentration in the tumor was below the detectable level until 24 h. These findings suggested that the highest specific accumulation of 5-FU in tumor cells may explain the best therapeutic results of UFT.

Administration, Oral↗
PubMed1994

In vivo 19F NMR comparative study of 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and an FT-uracil coadministration system in mouse tumors.

The suppression of alpha-fluoro-beta-alanine (FBAL) formation from 5-fluorouracil (FU) is an important subject in relation to tumor chemotherapy. This is the first comparative study of FU, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT, a prodrug of FU) and of FT+uracil as a coadministration system (UFT) under an oral dose using the in vivo 19F NMR method. The slow release of FU from FT and the suppression of the catabolism of FU to FBAL in mouse livers and tumors by the coadministration of uracil with FT were demonstrated using consecutive NMR measurements. The applicability of the in vivo 19F NMR method to the drug evaluation in tumors and livers of small animals was successfully tested.

Animals↗
PubMed1984

Cytochrome P-450-dependent oxidative cleavage of 1-(tetrahydro-2-furanyl)-5-fluorouracil to 5-fluorouracil.

Cytochrome P-450-dependent oxidative cleavage of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) was investigated in a reconstituted system containing purified phenobarbital-inducible cytochrome P-450 (P-450(1)) or 3-methylcholanthrene-inducible cytochrome P-450 (P-448(1)). FT was converted into 5-fluorouracil (5-FU) in the reconstituted system, and its rate was 71 pmol 5-FU formed/min/nmol P-4501 and 45 pmol 5-FU/min/nmol P-448(1). Cytochrome P-450, NADPH-cytochrome P-450 reductase and NADPH were required for 5-FU production. Inhibitors of cytochrome P-450 such as carbon monoxide and metyrapone markedly decreased the rate. FT was found to interact with the purified cytochrome P-450, causing a reverse type I spectral change. From these observations, we concluded that the hepatic microsomal cytochrome P-450-dependent mixed function oxidase system participates in the oxidative cleavage of FT.

Animals↗
PubMed1993

Mutagenic and clastogenic properties of (3-[3-(6-benzoyloxy-3-cyano-2- pyridyloxycarbonyl) benzoyl]-1-ethoxymethyl-5-fluorouracil) (BOF-A2), a new 5-fluorouracil derivative with anti-tumour activity.

As part of the safety assessment of (3-[3-(6-benzoyloxy-3-cyano-2- pyridyloxycarbonyl)benzoyl]-1-ethoxymethyl-5-fluorouracil) (BOF-A2), a new 5-fluorouracil (5-FU) derivative with anti-tumour activity, its potential genotoxicity was studied in 3 different tests. BOF-A2 was negative in a reverse mutation (Ames) test in strains of S. typhimurium and E. coli. BOF-A2 induced chromosomal aberrations in Chinese hamster cells in vitro especially in the presence of exogenous metabolic activation, and was clastogenic in vivo, inducing micronuclei in mouse bone marrow. The clastogenic activity of BOF-A2 was similar to that of 5-FU.

Animals↗