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At least 811 records · Page 45Linked to original sources
PubMed1997

Phase I studies of fluorouracil, doxorubicin and vinorelbine without (FAN) and with (SUPERFAN) folinic acid in patients with advanced breast cancer.

PURPOSE: The Breast Cancer Site Group of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG) undertook two parallel phase I studies to determine the maximum tolerated dose (MTD) and recommended phase II dose of vinorelbine in combination with doxorubicin and fluorouracil (with or without folinic acid) in metastatic breast cancer. METHODS: Cohorts of five patients were to receive: (a) fluorouracil 500 mg/m2 and doxorubicin 50 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on days 1, 8 and 15 every 3 weeks (FAN regimen), or (b) fluorouracil 340 mg/m2 and folinic acid 200 mg/m2 on days 1, 2, 3, 4 and 5, doxorubicin 40 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on day 1 and again on day 5 every 4 weeks (SUPERFAN regimen). Eligibility included measurable or evaluable metastatic breast cancer and having received neither previous chemotherapy for metastatic disease nor anthracycline-containing adjuvant therapy. RESULTS: Of 26 and 12 patients enrolled in the FAN and SUPERFAN regimens, 26 and 12 were evaluable for toxicity and 21 and 9 for response, respectively. Median ages were 60.3 years (41-71 years) and 64.2 years (51-73 years). Both regimens required amendment after the first cohort with an original day- 15 vinorelbine dose omitted from the FAN regimen and more prolonged nadir granulocyte counts allowed. Myelosuppression was dose limiting. MTDs in the FAN and SUPERFAN regimens were vinorelbine 25 mg/m2 and 20 mg/m2. Other toxicities included mucositis, septicemia and febrile neutropenia. Peripheral neuropathy and constipation were mild. Of the 21 FAN patients evaluable for response, 3 (14%) had complete responses and 7 (33%) had partial responses, for an overall response rate of 48%; 9 (43%) had stable disease and 2 (9%) had progressive disease as their best response. Of the nine SUPERFAN patients evaluable for response, none had a complete response. There were two (22%) with partial responses, and six (67%) had stable disease and one (11%) had progressive disease as their best response. CONCLUSIONS: The SUPERFAN regimen was too toxic to pursue even at the lowest dose. The recommended phase II starting dose for the FAN regimen was vinorelbine 20 mg/m2. Although these were phase I studies response rates in evaluable patients were less than expected and toxicity did not allow the use of as much vinorelbine in the combinations as had been anticipated. The limited response data from our study would imply that combining vinorelbine with more toxic agents may not enhance response rates and may defeat the advantage of tolerability, especially in elderly patients.

Adult↗
PubMed1999

A pharmacokinetic model and the clinical pharmacology of cis-platinum, 5-fluorouracil and mitomycin-C in isolated pelvic perfusion.

PURPOSE: An isolated pelvic perfusion technique using multiple agents was used both in patients with unresectable recurrent pelvic neoplasms and as a preoperative therapy for advanced pelvic malignancy. METHODS: The technique consisted of vascular occlusion via transfemoral balloon catheters, circulation and drug infusion using standard hemodialysis technology, and a 45-min isolation period. Blood and urine samples were analyzed for the levels of cis-platinum (17 patients, 21 courses of therapy, 50-100 mg/m2, infusion 0-10 min), 5-fluorouracil (12 patients, 14 courses, 1500 mg/m2, infusion 1/3 dose 0-1 min, 2/3 dose 1-20 min) and mitomycin-C (11 patients, 14 courses, 10-20 mg/m2, infusion 10-20 min). An empirical, four-compartment pharmacokinetic model was developed to establish drug distribution curves for the pelvic and systemic circulations and to yield valid estimates of the pharmacokinetic parameters. RESULTS: Pelvic isolation of drug was demonstrated by the pelvic-systemic drug exposure ratios of 6.0:1 for cis-platinum, 8.4:1 for 5-fluorouracil and 9.0:1 for mitomycin-C. Isolation at the L3-4 interspace resulted in minor urine drug elimination during isolation (cis-platinum 7.2% of drug, 5-fluorouracil 2.4% and mitomycin-C 2.5%). Because drug infusion was limited to the first 20 min of isolation, drug levels at the end of the isolation period were reduced to the extent that no extracorporeal drug removal mechanism was needed. CONCLUSION: These pharmacokinetic results indicate that this isolation technique has the potential to provide increased therapeutic indices and is a suitable system for evaluating fast-acting highly toxic experimental drugs to human pelvic cancers which are poorly responsive to conventional clinical protocols.

Antineoplastic Agents↗
PubMed2001

Combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin for metastatic urothelial cancer.

PURPOSE: To investigate the activity of combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin in patients with metastatic urothelial cancer. METHODS: A group of 29 patients were treated with 2000 mg/m2 ifosfamide, 750 mg/m2 5-fluorouracil, 100 mg/m2 etoposide and 20 mg/m2 cisplatin. All four drugs were given intravenously on days 1 through 3 and the treatment was repeated every 3 weeks. Of the 29 patients, 14 had lymph node metastasis alone, and 15 had visceral lesions. RESULTS: An objective response was achieved in 17 patients (59%). There was no difference in response rates according to metastatic site including osseous lesions, which responded well in four of six patients. The 3-year survival rate for all patients was 16% with four patients who had undergone salvage surgery being alive with no evidence of disease 15 to 61 months after initiation of the treatment. A good performance status, lymph node metastasis alone and administration of chemotherapy at the full dosage had a significantly favorable impact on patient survival. Bone marrow toxicity was significant and one patient died of treatment-related sepsis. CONCLUSIONS: Ifosfamide, 5-fluorouracil, etoposide and cisplatin combination chemotherapy appeared to be active in the treatment of metastatic urothelial cancer. Although bone marrow toxicity was significant, the treatment was well tolerated by the majority of the patients. Further study may be warranted.

Adult↗
PubMed2003

Ciliary body toxicity of cyclosporin A and octreotide acetate in rabbit eyes: a comparison with mitomycin C and 5-fluorouracil.

PURPOSE: To compare the toxicities of cyclosporin A, octreotide acetate, mitomycin C and 5-fluorouracil to the ciliary body. METHOD: We applied sponges soaked in these compounds to the open scleras of rabbit eyes. Histopathological specimens were obtained from the operation site and at 180 degrees from it on the 14th day after surgery. RESULTS: Mean ciliary epithelial thickness in the study groups was as follows: 12.29 +/- 2.69 microm in group 1 (mitomycin C), 13.85 +/- 4.56 microm in group 2 (5-fluorouracil), 17.71 +/- 3.09 microm in group 3 (cyclosporin A), 11.64 +/- 2.92 microm in group 4 (octreotide acetate), 11.92 +/- 2.89 microm in group 5 (topically applied octreotide acetate) and 21.85 +/- 4.29 microm in group 6 (control). The ciliary epithelial thickness in groups 1, 2, 4 and 5 was statistically different from that in the control group. Intracellular vacuolisation and degenerative changes of the non-pigmented epithelium, and pigment loss of the pigmented epithelium, were found mostly in group 1 and moderately in group 2 and 3. CONCLUSION: Octreotide acetate and cyclosporin A are less toxic alternatives to mitomycin C and 5-fluorouracil in glaucoma filtration surgery.

Animals↗
PubMed1999

5-ethyl-2'-deoxyuridine, a modulator of both antitumour action and pharmacokinetics of 5-fluorouracil.

The aim of the present studies was to elucidate the effects and optimal modulatory conditions of 5-ethyl-2'-deoxyuridine (EtdUrd) on the antitumour efficacy, pharmacokinetics and catabolism of 5-fluorouracil (5-FU) on Colon-26 and Colon-38 murine tumours. HPLC and GC-MS techniques were used to measure the concentrations of 5-FU, dihydro-5-fluorouracil, EtdUrd, 5-ethyluracil and uridine in the plasma and that of 5-FU and 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) in the tumours. It was shown that EtdUrd, given 1 h before 5-FU, selectively enhanced the antitumour action of 5-FU, without significantly increasing its toxic side-effects, thus resulting in an approximately three times higher therapeutic index. Pharmacokinetic studies revealed that 1 h after 400 mg/kg EtdUrd administration - i.e. at the time of 5-FU treatment - the plasma concentration of EtdUrd was 269 microM, and that of 5-ethyluracil, as the major metabolite of EtdUrd, was 421 microM. It is of interest that EtdUrd pretreatment did not change the maximal plasma concentration of 5-FU; however, the half-life of the terminal elimination increased from 114.5 min to 171.2 min and thus the mean residence time of 5-FU rose significantly (P < 0.05). After the combined treatment, the maximal concentration of dihydro-5-fluorouracil in the plasma decreased from 61.06 microM to 29.70 microM (P < 0.01). The intratumoral concentrations of 5-FU were 34%-158% higher 6-96 h after the combined treatment than after the single 5-FU treatment. EtdUrd also caused a moderate increase in the intratumoral level of FdUMP. It is noteworthy, that EtdUrd increased the endogenous uridine concentration in the plasma from 18 microM to a maximum of 249 microM, and the level remained high for longer than 6 h. The present studies indicate that EtdUrd enhances the therapeutic index of 5-FU by reducing the catabolism, prolonging the plasma and intratumoral concentrations of 5-FU and, at the same time, offering protection to normal organs by increasing the endogenous uridine level.

Animals↗
PubMed2001

Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer.

BACKGROUND: The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. METHODS: Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2, day 15), repeated at a 28-day interval, and followed by radical surgery. RESULTS: A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. CONCLUSIONS: Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate.

Adenocarcinoma, Scirrhous↗
PubMed2004

Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.

BACKGROUND: We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT). METHODS: Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2). RESULTS: A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group >> chemotherapy group >> control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups. CONCLUSION: The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).

Administration, Oral↗
PubMed2002

Topical treatment of Bowen's disease with 5-Fluorouracil.

BACKGROUND: Bowen's disease is a common skin cancer. There are many different therapeutic approaches to treatment. Topical 5-Fluorouracil (5-FU) cream has been used for many years and there are many published papers attesting to its effectiveness. However, no papers have presented long-term followup results with biopsy confirmation of cure. OBJECTIVES: The purpose of this article is to present the long-term findings following the use of this cream in the treatment of Bowen's disease. METHODS: Twenty-four patients with 26 biopsy-confirmed lesions of Bowen's disease were treated with topical 5-Fluorouracil cream and were followed for periods of up to 10 years. Posttreatment biopsies were performed in most cases. RESULTS: Two of the 26 lesions treated topically recurred at some point. The rest were apparently cured. CONCLUSION: The results presented in this article confirm that treatment of Bowen's disease with topical 5-Fluorouracil cream is safe and effective treatment.

Aged↗
PubMedDate not supplied

Neoadjuvant chemotherapy with P-ELF (cisplatin, etoposide, leucovorin, 5-fluorouracil) followed by radical resection in patients with initially unresectable gastric adenocarcinoma: a phase II study.

BACKGROUND: Gastric cancer is the most frequent gastrointestinal cancer in Mexico. Only 33% of cases are resectable. Our aim was to determine the activity and toxicity of the cisplatin, etoposide, leucovorin, and 5-fluorouracil combination in initially unresectable tumors and to determine its ability to permit resection. METHODS: Sixty patients with unresectable gastric adenocarcinoma were treated with cisplatin 80 mg/m2, etoposide 80 mg/m2, leucovorin 25 mg/m2, and 5-fluorouracil 800 mg/m2 by central intravenous catheter for 4 consecutive days. Two courses of this combination were followed by surgical resection. RESULTS: The overall response rate was 36.8% (20 partial responses and one complete response). By using logistic regression analysis, the tumor, node, and metastasis stage (risk ratio, 2.04; 95% confidence interval, 1.03-4.02; P = .039) was identified as the response determinant to chemotherapy. Major toxicity was grade 3 or 4 neutropenia in 67% of patients. Ten resections were performed (17.5%); five were curative and five palliative. Operative morbidity and mortality rates were 40% and 10%, respectively. The median length of survival was 7.46 and 13.3 months for nonresponders and responders, respectively (P = .011). CONCLUSIONS: The cisplatin, etoposide, leucovorin, and 5-fluorouracil combination is active in advanced gastric cancer and the toxicity level is acceptable. This treatment permits a 17.5% resection rate in previously unresectable tumors. A randomized trial of surgery vs. neoadjuvant chemotherapy plus surgery is warranted.

Adenocarcinoma↗
PubMed1987

Prinzmetal's angina during 5-fluorouracil chemotherapy.

Variant angina developed during intravenous 5-fluorouracil therapy in a patient without prior history of angina pectoris. Ambulatory electrocardiography demonstrated S-T segment elevation and ventricular ectopy during pain, whereas no symptoms or S-T segment changes occurred during placebo therapy. Prophylaxis with both nifedipine and diltiazem was successful in preventing recurrence. It is believed that 5-fluorouracil induced coronary vasospasm and that this was prevented by prophylactic calcium antagonist therapy. Drug-induced coronary artery spasm may be the cause of 5-fluorouracil-associated chest pain.

Angina Pectoris, Variant↗
PubMed1983

5-Fluorouracil in the treatment of acute pancreatitis.

The present data show that treatment with 5-fluorouracil may be of some benefit, but the results are not at all as convincing or promising as those previously reported in clinical and experimental trails. One possible explanation is that the dose of 5-fluorouracil was too small. However, Russian clinical studies have reported good results with identical doses. Their very good results were not confirmed in this study. Another explanation is that 5-fluorouracil should have been administered at an earlier phase of acute pancreatitis, which is not possible in clinical studies. This may explain the good results achieved in experimental trials.

Acute Disease↗
PubMed1984

Mechanism of inhibition of phosphoribosylation of 5-fluorouracil by purines.

The mechanism of the abolishment of the cytotoxicity of 5-flurouracil by purines in L5178Y cells was determined by using phosphoribosylation enzymes for both 5-fluorouracil and hypoxanthine. Hypoxanthine inhibited the phosphoribosylation of 5-fluorouracil in the presence of both enzymes, but no inhibition by hypoxanthine was found without hypoxanthine phosphoribosyltransferase or at a high concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP). Hypoxanthine, adenine and inosine decreased the intracellular concentration of PRPP to less than one-tenth of that of the control. These results suggest that 5-fluorouracil is activated directly to its nucleotide, 5-fluorouridine 5'-monophosphate, by the phosphoribosylation enzyme and that the inhibition of activation by purines is due to depletion of PRPP.

Animals↗
PubMed1995

Population characteristics of hepatic dihydropyrimidine dehydrogenase activity, a key metabolic enzyme in 5-fluorouracil chemotherapy.

Dihydropyrimidine dehydrogenase is the initial rate-limiting enzyme in catabolism of 5-fluorouracil, one of the most widely used cancer chemotherapeutic agents. Previous studies have shown the clinical importance of determination of dihydropyrimidine dehydrogenase in patients with cancer, particularly in those with deficiency of this enzyme who experience severe 5-fluorouracil-associated toxicity (including death) after 5-fluorouracil treatment. In the present study, dihydropyrimidine dehydrogenase activity was determined in 138 donor liver samples. A normal distribution of human liver dihydropyrimidine dehydrogenase activity was shown. The mean enzyme activity was compared across different groups by age, gender, and race, with no significant differences observed except that the mean enzyme activity in women was slightly higher than that observed in men. With use of a polyclonal antibody generated against human liver dihydropyrimidine dehydrogenase, Western blot analysis showed that dihydropyrimidine dehydrogenase protein in the liver cytosol correlated with the activity of this enzyme.

Adult↗
PubMed1987

Mobility of individual 5-fluorouridine residues in 5-fluorouracil-substituted Escherichia coli valine transfer RNA. A 19F nuclear magnetic resonance relaxation study.

19F nuclear magnetic resonance (n.m.r.) relaxation parameters of 5-fluorouracil-substituted Escherichia coli tRNA(Val)1 were measured and used to characterize the internal mobility of individual 5-fluorouridine (FUrd) residues in terms of several models of molecular motion. Measured relaxation parameters include the spin-lattice (T1) relaxation time at 282 MHz, the 19F(1H) NOE at 282 MHz, and the spin-spin (T2) relaxation time, estimated from linewidth data at 338 MHz, 282 MHz and 84 MHz. Dipolar and chemical shift anisotropy contributions to the 19F relaxation parameters were determined from the field-dependence of T2. The results demonstrate a large chemical shift anisotropy contribution to the 19F linewidths at 282 and 338 MHz. Analysis of chemical shift anisotropy relaxation data shows that, relative to overall tumbling of the macromolecule, negligible torsional motion occurs about the glycosidic bond of FUrd residues in 19F-labeled tRNA(Val)1, consistent with the maintenance of base-base hydrogen-bond and/or stacking interactions at all fluorouracil residues in the molecule. The dipolar relaxation data are analyzed by using the "two-state jump" and "diffusion in a cone" formalisms. Motional amplitudes (theta) are interpreted as being due to pseudorotational fluctuations within the ribose ring of the fluorinated nucleoside. These amplitudes range from approximately 30 degrees to 60 degrees, assuming a correlation time (tau i,2) of 1.6 ns. By using available 19F n.m.r. assignment data for the 14 FUrd residues in 5-fluorouracil-substituted tRNA(Val)1, these motional amplitudes can be correlated directly with the environmental domain of the residue. Residues located in tertiary and helical structural domains show markedly less motion (theta approximately equal to 30 to 35 degrees) than residues located in loops (theta approximately equal to 45 to 60 degrees). A correlation between residue mobility and solvent exposure is also demonstrated. The amplitudes of internal motion for specific residues agree quite well with those derived from X-ray diffraction and molecular dynamics data for yeast tRNA(Phe).

Chemical Phenomena↗
PubMed1987

19F nuclear magnetic resonance as a probe of anticodon structure in 5-fluorouracil-substituted Escherichia coli transfer RNA.

The use of 19F nuclear magnetic resonance (n.m.r.) spectroscopy as a probe of anticodon structure has been extended by investigating the effects of tetranucleotide binding to 5-fluorouracil-substituted Escherichia coli tRNA(Val)1 (anticodon FAC). 19F n.m.r. spectra were obtained in the absence and presence of different concentrations of oligonucleotides having the sequence GpUpApX (X = A,G,C,U), which contain the valine codon GpUpA. Structural changes in the tRNA were monitored via the 5-fluorouracil residues located at positions 33 and 34 in the anticodon loop, as well as in all other loops and stems of the molecule. Binding of GpUpApA, which is complementary to the anticodon and the 5'-adjacent FUra 33, shifts two resonances in the 19F spectrum. One, peak H (3.90 p.p.m.), is also shifted by GpUpA and was previously assigned to FUra 34 at the wobble position of the anticodon. The effects of GpUpApA differ from those of GpUpA in that the tetranucleotide induces the downfield shift of a second resonance, peak F (4.5 p.p.m.), in the 19F spectrum of 19F-labeled tRNA(Val)1. Evidence that the codon-containing oligonucleotides bind to the anticodon was obtained from shifts in the methyl proton spectrum of the 6-methyladenosine residue adjacent to the anticodon and from cleavage of the tRNA at the anticodon by RNase H after binding dGpTpApA, a deoxy analog of the ribonucleotide codon. The association constant for the binding of GpUpApA to fluorinated tRNA(Val)1, obtained by Scatchard analysis of the n.m.r. results, is in good agreement with values obtained by other methods. On the basis of these results, we assign peak F in the 19F n.m.r. spectrum of 19F-labeled tRNA(Val)1 to FUra 33. This assignment and the previous assignment of peak H to FUra 34 are supported by the observation that the intensities of peaks F and H in the 19F spectrum of fluorinated tRNA(Val)1 are specifically decreased after partial hydrolysis with nucleass S1 under conditions leading to cleavage in the anticodon loop. The downfield shift of peak F occurs only with adenosine in the 3'-position of the tetranucleotide; binding of GpUpApG, GpUpApC, or GpUpApU results only in the upfield shift of peak H. The possibility is discussed that this base-specific interaction between the 3'-terminal adenosine and the 5-fluorouracil residue at position 33 involves a 5'-stacked conformation of the anticodon loop. Evidence also is presented for a temperature-dependent conformational change in the anticodon loop below the melting temperature of the tRNA.

Anticodon↗
PubMed1988

Evaluation of bolus cis-platinum and continuous 5-fluorouracil infusion for metastatic and recurrent squamous cell carcinoma of the cervix.

The combination of cis-platinum and 5-fluorouracil has been reported to act synergistically with improved response rates in squamous cell carcinomas of the head and neck. The activity of bolus cis-platinum and continuous infusion of 5-fluorouracil in 24 patients with recurrent and metastatic squamous cell carcinoma of the cervix was evaluated. Twelve patients were stage I, 3 were stage II, 5 were stage III, and 4 were stage IV cervical carcinomas. Among the 24 patients, there were 4 complete and 8 partial responses (50%). The overall median response was 24 weeks. The overall cumulative survival was 55% at 40 weeks and 40% at 1 year after beginning this regimen. Complications included 4 patients who developed leukopenia, 3 thrombocytopenia, 11 stomatitis, 14 nephrotoxicity, 4 peripheral neuropathy, and 6 ototoxicity. The combination of cis-platinum and continuous infusion of 5-fluorouracil appears to have useful activity in patients with recurrent or metastatic squamous cell carcinoma of the cervix.

Adult↗
PubMed1989

A phase II evaluation of cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the cervix: a Gynecologic Oncology Group Study.

Cisplatin is one of the most active single agents in advanced squamous cell carcinoma of the cervix and is synergistic with 5-fluorouracil in the laboratory. The Gynecologic Oncology Group has conducted a phase II trial in which cisplatin at 50 mg/ml2 given intravenously on Day 1 was combined with 5-fluorouracil 1000 mg/m2 daily given as a 24-hr infusion on Days 1-5. Treatment was repeated every 21 days. Fifty-five patients were treated with this regimen, resulting in seven complete remissions (12.7%) and five partial remissions (9.1%). The median survival was 6.4 months. Toxic effects of grade 2 or greater were leukopenia in 10 patients (18.2%), thrombocytopenia in 2 patients (3.6%), gastrointestinal effects in 25 patients (45.5%), and renal effects in 1 patient (1.8%). On the basis of these results, the cisplatin and 5-fluorouracil regimen does not appear to have any advantage over cisplatin alone in advanced cervical cancer.

Adult↗
PubMed1996

Inhibition of replication of rinderpest virus by 5-fluorouracil.

5-Fluorouracil (5FU), an analogue of uracil, was found to inhibit the production of infectious particles of rinderpest virus (RPV) in Vero cells (African green monkey kidney cells) by 99%, at a concentration of 1 microgram/ml. The levels of individual mRNA specific for five of the virus genes were also reduced drastically, while the level of mRNA for a cellular housekeeping gene-glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-was unaltered by fluorouracil treatment of infected cells. Both virus RNA and protein synthesis showed inhibition in a dose-dependent manner. The virions which budded out of 5-fluorouracil-treated cells also contained reduced amounts of virus proteins compared with virus particles from untreated cells.

Animals↗