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PubMed2005

Adjuvant interleukin-2, interferon-alpha, and 5-fluorouracil immunochemotherapy after radical nephrectomy for locally advanced renal cell carcinoma.

OBJECTIVES: To investigate the efficacy of interleukin-2 (IL-2), interferon-alpha, and 5-fluorouracil combination immunochemotherapy as adjuvant therapy after radical nephrectomy for nonmetastatic pathologic Stage T3 renal cell carcinoma. METHODS: Thirty patients who underwent radical nephrectomy for pT3N0M0 renal cell carcinoma at our department from June 1999 to December 2003 were studied retrospectively. Of the 30 patients, 9 (adjuvant group) also received adjuvant interleukin-2, interferon-alpha, and 5-fluorouracil immunochemotherapy after surgery; the other 21 (nonadjuvant group) did not. A comparative analysis of the two groups was performed with respect to disease-free and overall survival. Side effects from immunochemotherapy were also assessed. RESULTS: The adjuvant therapy and nonadjuvant therapy groups were not significantly different with respect to age, sex, Eastern Cooperative Oncology Group performance status, pathologic subtype, pathologic stage, tumor size, and Fuhrman's grade. The two groups demonstrated a significant difference in the time to progression (log-rank test, P = 0.011). Although 3 patients had died at a mean follow-up of 23.8 months (range 7.5 to 35) in the nonadjuvant group, apparent differences between the two groups in overall survival were not statistically significant (log-rank test, P = 0.2487). Combination immunochemotherapy was mostly well tolerated, and all side effects were limited to World Health Organization grades 1 and 2. CONCLUSIONS: Despite the ongoing controversy surrounding its effectiveness in the treatment of metastatic renal cell carcinoma, the results of our preliminary study suggest that interleukin-2, interferon-alpha, 5-fluorouracil combination immunochemotherapy may be effective as adjuvant therapy after complete resection of pT3N0M0 renal cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Primate trabeculectomies with 5-fluorouracil collagen implants.

Bilateral trabeculectomies were performed on four normal cynomolgus monkeys. Highly purified bovine skin collagen implants with either 1 mg of 5-fluorouracil or physiologic saline (one each per monkey by randomized, masked assignment) were sutured under the scleral flaps. The randomization code was not broken until all clinical and histopathologic observations had been completed. Six weeks postoperatively, the 5-fluorouracil-treated eyes had more deeply open internal trabeculectomy ostia than the control eyes; however, the intraocular pressures were indistinguishable, the filtering blebs were only minimally different, and half of each group had trace or mild anterior subcapsular lenticular changes. Histologically, a multinucleated foreign body giant cell reaction was evident in all of the collagen implants, but the 5-fluorouracil-treated eyes had less vigorous or delayed reactions compared to the control eyes. The collagen implant appears to be a poor drug delivery system in this model of glaucoma filtering surgery, because it incites a granulomatous inflammatory reaction.

Animals↗
PubMed1983

Toxic effect of fluorouracil on the rabbit retina.

We conducted electrophysiologic tests of the toxic effects of fluorouracil on 26 albino rabbit eyes. Fluorouracil concentrations of 10(-7) g/ml, 10(-6) g/ml, and 10(-5) g/ml produced no significant changes in the b-wave amplitudes of the electroretinogram. A concentration of 10(-4) g/ml, however, reduced the b-wave amplitude to 62% +/- 7.3% of the original value after 60 minutes. A concentration of 10(-3) g/ml decreased the value even further, to 41% +/- 12% of the original value. At this concentration the a-wave appeared to be enhanced, probably because the ascending phase of the b-wave was delayed. A concentration of 5 X 10(-3 g/ml resulted in disappearance of the b-wave within approximately three minutes, but removal of the test solution and replacement with a fluorouracil-free medium produced recovery of the b-wave amplitude to 89% +/- 9.9% of the original value within 55 minutes.

Animals↗
PubMed1987

Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil.

We studied four patients who, having received postoperative 5-fluorouracil after glaucoma filtering operations, developed serious corneal complications. All four patients had preexisting corneal abnormalities including keratoconjunctivitis sicca, exposure keratopathy, and bullous keratopathy. All of the patients developed epithelial defects in the postoperative period. The complications included bacterial corneal ulceration (two patients), sterile corneal ulceration and corneal perforation (one patient), and a keratinized corneal plaque with underlying sterile stromal infiltrate (one patient). The use of 5-fluorouracil, which is an antimetabolite with considerable corneal epithelial toxicity, after glaucoma filtering surgery frequently causes corneal epithelial defects that may lead to secondary complications. Patients receiving this drug should have their corneal status closely monitored. In patients with corneal epithelial disease, 5-fluorouracil should be used with caution.

Aged↗
PubMed1990

Trabeculectomy with 5-fluorouracil for adult inflammatory glaucoma.

We reviewed the records of 12 eyes of ten adult patients with inflammatory glaucoma who underwent trabeculectomy with the adjuvant use of 5-fluorouracil between January 1986 and January 1989. Intraocular pressure decreased from 36 +/- 10 mm Hg (range, 17 to 50 mm Hg) preoperatively to 11 +/- 4 mm Hg (range, 3 to 17 mm Hg) postoperatively after a median follow-up of 7.75 months (range, six to 38 months). All eyes achieved an intraocular pressure of less than 20 mm Hg, and ten of 12 required no intraocular pressure lowering medications. The mean (+/- S.D.) amount of 5-fluorouracil used was 33 +/- 10 mg (range, 20 to 55 mg). During the period of observation, five of 12 eyes had an episode of uveitis, but in no patient did this result in loss of intraocular pressure control. Preoperative and postoperative systemic and topical corticosteroid use was the same. Trabeculectomy with 5-fluorouracil is an effective treatment for selected cases of adult inflammatory glaucoma refractory to medical management.

Adult↗
PubMed1992

Effect of 5-fluorouracil on interleukin-2 expression.

The effect of 5-fluorouracil on the expression of IL-2 gene and the production of IL-2 protein has been studied using spleenic lymphocytes of rats. The IL-2 messenger RNA has been quantitated by dot-blots and IL-2 has been assayed by Con A-blast assay. The results show that there is up to 3.75 fold increase in the production of IL-2 message in 5-fluorouracil treated lymphocytes over Con A treated controls. There is also a concomitant increase in IL-2 protein production upon 5-fluorouracil treatment in rat lymphocytes.

Animals↗
PubMed1999

Interferon-alpha and 5-fluorouracil therapy in patients with metastatic renal cell cancer: an open multicenter trial. The Japanese Study Group Against Renal Cancer.

OBJECTIVES: Recent clinical trials have implied the cytotoxic and antiproliferative effects of combining 5-fluorouracil and interferon-alpha in the treatment of metastatic renal cell cancer. We therefore conducted an open multicenter trial to test the efficacy of such a combination on this cancer. METHODS: Human lymphoblastoid interferon (3 MIU per patient) was administered subcutaneously three times weekly for 12 weeks, while 5-fluorouracil was administered (600 mg/m2/day) as a continuous infusion for the first 5 days, followed by an intravenous bolus infusion of 600 mg/m2 once a week from the 3rd week until the 12th week. RESULTS: Of the 63 patients entered into the trial, 55 were eligible and evaluable for systemic toxicities, and 53 were evaluable for their response. All patients had undergone a prior nephrectomy, and their European Cooperative Oncology Group (ECOG) performance status ranged from 0 to 3 (median 0). Three complete and eight partial responses were induced, with an overall response rate of 20.0%. The median time to progression and the median survival time were 11 and 33 months, respectively. World Health Organization grade 3 toxicities were observed in 8 patients; however, no grade 4 toxicities or toxicity-related deaths were noted. CONCLUSIONS: Combination therapy of interferon-alpha plus 5-fluorouracil at the above-described dosage and schedule produced no better responses than interferon monotherapies. Prolongation of survival could be attributable to the fair performance status of the patients. This regimen has limited value for the treatment of patients with advanced renal cell cancer.

Adult↗
PubMed2002

Long-term follow-up of initially successful trabeculectomy with 5-fluorouracil injections.

PURPOSE: To study the long-term results (1-14 years) of trabeculectomies with 5-fluorouracil injections that were successful at 1 year. DESIGN: A retrospective noncomparative case series. INTERVENTION/PARTICIPANTS: We identified 87 patients (87 eyes) who had trabeculectomies with 5-fluorouracil injections from 1984 to 1989 that were successful at 1 year and had a follow-up range of 1.0 to 14.7 years (mean, 8.1, standard deviation of 4.4 years). All patients had previously failed glaucoma surgery (66.7%), cataract surgery (47.1%), or other diagnoses making them at high risk for failure. MAIN OUTCOME MEASURES: Successful control of intraocular pressure (IOP) was defined as IOP less than 21 mmHg or a reduction of 33% if preoperative pressure was less than 21 mmHg. Statistical analysis was performed using Kaplan-Meier life table analysis. RESULTS: If an eye is considered successful by IOP at 1 year, the probability of successful control is 61% at 5 years, 44% at 10 years, and 41% at 14 years. CONCLUSIONS: Despite successful IOP control at 1 year, trabeculectomies with 5-fluorouracil injections show a continual loss of IOP control over time.

Adolescent↗
PubMed1984

5-fluorouracil: new applications in complicated retinal detachment for an established antimetabolite.

Long-term reattachment of the retina following the development of proliferative vitreoretinopathy is often prevented by the occurrence of cellular reproliferation. 5-fluorouracil, a synthetic pyrimidine analog, is a potent inhibitor of fibroblast proliferation in cell culture and an animal model of tractional retinal detachment. Doses of up to 1.0 mg, when administered intravitreally to rabbits, result in no demonstrable retinal toxicity by microscopic and electrophysiologic criteria. The first 22 consecutive patients with advanced forms of proliferative vitreoretinopathy were treated with a combination of periocular and intraocular 5-fluorouracil, in addition to scleral buckling and vitrectomy. Retinal reattachment was achieved in 60% of patients at 6 months postoperatively. No serious systemic or ocular complications were observed although delayed healing of corneal epithelial defects occurred in 18% of cases and subtle subepithelial scarring in 31.8%. In combination with standard vitrectomy techniques, post-operative fluid gas exchange, and photocoagulation, periocular and subconjunctival 5-fluorouracil appears to improve the prognosis for longterm retinal reattachment following the development of proliferative vitreoretinopathy.

Adolescent↗
PubMed1986

Weekly pulse dosing schedule of fluorouracil: a new topical therapy for psoriasis.

We report use of a new weekly pulse dosing schedule of 5% fluorouracil under occlusion for topical treatment of recalcitrant psoriasis. This schedule eliminates the severe local toxicity reported in continuous dosing schedules. The thirteen outpatients completing this study were given continuous topical application of fluorouracil for a mean of 2 to 3 days per week; mean duration of therapy was 15.7 weeks. Eleven patients had an average of 90% clearing of actively treated lesions; 6% clearing was obtained with placebo. At 3-month follow-up examination, improvement was maintained in five patients, was maintained by at least 50% in two, and was lost in four. The five patients with remission at 3 months reported continued remission for up to an additional 8 months. This pulse dosing schedule makes topical fluorouracil under occlusion a useful, safe treatment for limited plaque psoriasis that does not respond to topical corticosteroid therapy.

Administration, Topical↗
PubMed1987

Role of preoperative topical 5-fluorouracil in preparation for Mohs micrographic surgery of extramammary Paget's disease.

The true extent of the skin affected in extramammary Paget's disease is frequently well beyond its clinical borders. A case of extramammary Paget's disease of the scrotum was treated with Mohs micrographic surgery. Prior to surgery, 5-fluorouracil was applied topically for 10 days. This resulted in a sharply delineated, erythematous patch of biopsy-proved extramammary Paget's disease well beyond the original clinical borders. This increased the visible area of disease by 60%. Mohs micrographic surgery detected microscopic extramammary Paget's disease approximately 1 cm beyond the erythematous borders. The location of disease farthest from the margins was in the direction toward which this erythema was most advanced when the application of 5-fluorouracil was discontinued. At the time of writing, 3.5 years after treatment, the patient was free of disease. Topical 5-fluorouracil may have a role as an adjunct to surgery by highlighting subclinical areas of extramammary Paget's disease. It may also be useful postoperatively to detect early disease recurrence.

Aged↗
PubMed1997

Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin.

BACKGROUND: Disseminated actinic keratoses are a therapeutic problem. OBJECTIVE: Our purpose was to evaluate the efficacy of a combination of topical 5-fluorouracil twice a day and 20 mg of oral isotretinoin daily for disseminated actinic keratoses. METHODS: Twenty-seven patients who had disseminated actinic keratoses (3 women, 24 men) were treated with 5-fluorouracil (5%) twice a day applied to the photodamaged area bearing actinic keratoses along with oral isotretinoin, 20 mg daily. The median treatment time was 21 days. RESULTS: Actinic keratoses disappeared and signs of photodamaged skin improved in all patients. Side effects were burning and itching as well as painful erosions during the final stage of treatment. CONCLUSION: The combination of topical 5-fluorouracil and isotretinoin is highly effective in the treatment of disseminated actinic keratoses on photodamaged skin.

Administration, Oral↗
PubMed1978

Therapeutic consequences of antitumour drug interactions: methotrexate and 5-fluorouracil in the chemotherapy of C3H mice with transplanted mammary adenocarcinoma.

Methotrexate and 5-fluorouracil at fixed dosages of 1.5 mg/kg and 50 mg/kg, respectively, were employed in combination chemotherapy for transplanted mammary adenocarcinoma in C3H mice. Tumour regression analyses demonstrated the importance of drug sequence and scheduling. Significantly, a drug synergism and antagonism was exhibited under certain conditions. Results indicated a superior therapeutic efficacy when methotrexate was administered 6-12 h before 5-fluorouracil; the reverse proved antagonistic. However, at longer intervals a commutative additivity was apparent. Judicious scheduling of methotrexate and 5-fluorouracil would seem appropriate, as both drugs are widely employed in the current management of neoplasms, such as breast carcinoma.

Adenocarcinoma↗
PubMed2002

Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil and cisplatin for T4 esophageal cancer with or without fistula.

PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. CONCLUSION: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas.

Aged↗
PubMed2003

Mature survival results with preoperative cisplatin, protracted infusion 5-fluorouracil, and 44-Gy radiotherapy for esophageal cancer.

PURPOSE: To assess the long-term survival results after cisplatin, protracted infusion 5-fluorouracil, and concurrent radiotherapy (RT) followed by surgical resection of esophageal cancer. METHODS AND MATERIALS: Ninety-two patients with esophageal cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) were treated in two sequential protocols of preoperative chemoradiotherapy. The patients had tumor confined to the esophagus and regional nodes, including celiac nodes for middle and distal lesions. In trial A (1989-1994), 50 patients were treated with 44 Gy RT (2 Gy/d) along with concurrent 5-fluorouracil 300 mg/m(2)/d given by protracted venous infusion on Days 1-30 and cisplatin 26 mg/m(2) on Days 1-5 and 26-30. In trial B (1995-1997, 42 patients), the chemotherapy dosages during RT were reduced to 5-fluorouracil 225 mg/m(2)/d protracted venous infusion and cisplatin 20 mg/m(2)/d on Days 1-5 and 16-30; three cycles of paclitaxel 135 mg/m(2)and cisplatin 75 mg/m(2) were given postoperatively. Surgery generally occurred 4-6 weeks after completion of the planned preoperative therapy. Transhiatal resection was performed whenever possible. RESULTS: Of the 92 patients, 86 (93%) underwent surgery (1 refused, 2 died preoperatively, and 3 developed evidence of metastatic disease). Of the 92 patients, 80 (87%) had complete resections with negative margins (3 had positive margins and 3 had distant metastases discovered at surgery). The pathologic complete response rate was 33% (30 of 92). The median follow-up was 63.5 months. The median survival and disease-specific survival for all enrolled patients was 35 and 59 months, respectively. The 5-year survival and disease-specific survival rate was 40% and 49%, respectively. Patients with a pathologic complete response had a 67% survival rate at 5 years (median not reached), and the remainder of patients had a 5-year survival rate of 27% (median 21 months; p <0.001). For 21 patients alive after 5 years (60-121 months), 2 died of their disease and all others were disease free. Eight patients with pathologic Stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy. The median survival for patients with pathologic Stage IIA, IIB, III, and IV disease at the time of surgery was 22, 13.5, 18, and 4.9 months, respectively. The pattern of initial failure was local/regional alone in 6% (5 of 90), local/regional plus distant in 3% (3 of 90), and distant alone in 47% (42 of 90). No differences were noted in survival or response rate between those with adenocarcinoma or squamous cell carcinoma. CONCLUSION: The promising 5-year survival results and low rate of late cancer-related deaths suggest that these regimens of intensive neoadjuvant therapy may improve the overall cure rate. The pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for novel adjuvant therapies. Isolated local failure is uncommon, indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the RT. Additional randomized data are needed to assess the benefits of this therapeutic approach fully.

Adenocarcinoma↗
PubMed1997

Determination of S-1 (combined drug of tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate) and 5-fluorouracil in human plasma and urine using high-performance liquid chromatography and gas chromatography-negative ion chemical ionization mass spectrometry.

A high-performance liquid chromatography (HPLC) and gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICI-MS) method was developed for the analysis of the combined antitumor drug S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate) and active metabolite 5-fluorouracil in human plasma and urine. Tegafur was fractionated from biological fluids by extraction with dichloromethane and analyzed by HPLC. 5-Fluorouracil and 5-chloro-2,4-dihydroxypyridine were extracted with ethyl acetate from the residual layer after extraction of tegafur, and converted to pentafluorobenzyl (PFB) derivatives. Potassium oxonate was cleaned up with an anion-exchange column (Bond Elut NH2). The extracted potassium oxonate was degraded to 5-azauracil and converted to PFB derivatives. The PFB derivatives were analyzed by GC-NICI-MS. A stable isotope was employed as the internal standard in the GC-NICI-MS analysis. The limits of quantitation of tegafur, 5-fluorouracil, 5-chloro-2,4-dihydroxypyridine and potassium oxonate in plasma were 10, 1, 2 and 1 ng/ml, respectively. The reproducibility of the analytical method according to the statistical coefficients is approximately 10%. The accuracy of the method is good; that is, the relative error is < 10%. The methods were applied to pharmacokinetic studies of S-1 in patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study.

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.

Adult↗
PubMed1993

Prednimustine (Sterecyt) versus cyclophosphamide both in combination with methotrexate and 5-fluorouracil in the treatment of advanced breast cancer.

153 women with advanced breast cancer were randomly allocated for treatment with SMF [prednimustine (Sterecyt) + methotrexate + 5-fluorouracil, 83 patients] or CMF (cyclophosphamide+methotrexate+5-fluorouracil, 70 patients). Prednimustine was administered orally 100 mg/m2 daily, for 5 days, and cyclophosphamide was administered orally 100 mg/m2, for 14 days, each, every 4 weeks. Methotrexate was given at a dose of 40 mg/m2 and 5-fluorouracil at 600 mg/m2 on day 1 and 8, every 4 weeks. Leucovorin was used in 39 patients to alleviate mucositis. The two treatment groups were balanced in terms of age, performance status, lymph node status, histology, menopausal status and previous therapy. Response was evaluated in 140 patients. Of 76 patients treated with SMF, 4 had a complete and 21 a partial response (CR+PR = 33%), 40 had no change (NC) and 11 had progressive disease (PD). Of 64 patients treated with CMF, 3 had a complete and 18 a partial response (CR+PR = 33%), 30 had no change (NC) and 13 had progressive disease (PD). Time to treatment failure and survival were similar in both groups. A relationship between haematological and gastrointestinal toxicity and therapeutic efficacy was demonstrated with a superior survival and response rate recorded for patients with such toxicity than in patients without. Haematological toxicity was, in general, mild to moderate with no difference between the two groups. Alopecia (P = 0.008), nausea/vomiting (P = 0.02) and euphoria (P = 0.03) were more common in the CMF-treated group. Diarrhoea was more common in the SMF group (P = 0.03). In conclusion, SMF seems to be as efficient as CMF with regard to response rate, time to treatment failure and survival. However, SMF was tolerated better than CMF.

Antineoplastic Combined Chemotherapy Protocols↗