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Amifostine, in a reduced dose, protects against severe diarrhea associated with weekly fluorouracil and folinic acid chemotherapy in advanced colorectal cancer: a pilot study.

Fifty-two consecutive patients with advanced colorectal cancer who developed persistent diarrhea following chemotherapy with 5-fluorouracil despite dose reduction were treated with amifostine 800, 500 or 150 mg/m(2). The administered dose of 5-fluorouracil was significantly greater during amifostine treatment. Amifostine 800 mg/m(2) was associated with complete elimination of diarrhea, but 76.3% of patients developed infusion-related hypotension. At a dose of 500 mg/m(2), diarrhea was significantly reduced and milder compared with baseline and the incidence of hypotension was 54.2%. At the lowest dose of amifostine, 17.1% of patients developed Grade 1 diarrhea, a significant reduction over baseline, and hypotension occurred in 25.2% of patients. Treatment with amifostine also improved mucositis but had no effect on the relatively mild nausea and vomiting due to 5-fluorouracil. In this study, amifostine reduced the incidence and severity of diarrhea associated with 5-fluorouracil in patients with advanced colorectal cancer, with acceptable efficacy at a reduced dose that offered better tolerability.

Aged↗

In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets.

The objective of the present study is to compare the guar gum-based colon-targeted tablets of 5-fluorouracil against an immediate release tablet by in vitro dissolution and in vivo pharmacokinetic studies in human volunteers. Twelve healthy volunteers participated in the study. 5-Fluorouracil was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablet. On oral administration of colon-targeted tablets, 5-fluorouracil started appearing in the plasma at 6 h, and reached the peak concentration (C(max) of 216+/-15 ng/ml) at 7.6+/-0.1 h (T(max)), whereas the immediate release tablets produced peak plasma concentration (C(max) of 278+/-21 ng/ml) at 0.6+/-0.01 h (T(max)). The AUC(0- infinity ) for 5-fluorouracil from colon-targeted tablet and immediate release tablet were found to be 617+/-39 and 205+/-21 ng/ml/h, respectively. Colon-targeted tablets showed delayed t(max), delayed absorption time (t(a)), decreased C(max) and decreased absorption rate constant when compared to the immediate release tablets. The results of the study indicated that the guar gum-based colon-targeted formulation did not release the drug in stomach and small intestine, but delivered it to the colon resulting in a slow absorption of the drug and making it available for local action in colon.

Adolescent↗

Phase II trial of cisplatin, 5-fluorouracil, and interferon-alpha-2B as first line treatment of advanced urothelial cancer.

Cisplatin based combination chemotherapy remains the mainstay for treatment of advanced urothelial cancer. The combination of 5-fluorouracil and interferon has been found to be effective second line treatment of advanced urothelial cancer. Hence, we tested the combination of cisplatin, 5-fluorouracil and interferon as first line therapy in advanced urothelial cancer. Eligible patients had to have no prior chemotherapy or interferon. Treatment consisted of cisplatin 80 mg/m(2) on day one, followed by 5-fluorouracil 750 mg/m(2) as a daily infusion for 5 days and interferon alpha 2 B 5 MU/m(2) subcutaneously daily on day 1-5 of 5-fluorouracil infusion. Cycles repeated every 21 days. Eighteen patients, of which sixteen were males were enrolled. Median age was 60 years. All patients had transitional-cell carcinoma. The median number of cycles given was 4. Thirteen patients were evaluable for response. Two patients achieved CR and 3 PR for an overall response rate of 28% (95% confidence interval 7% to 49%). Median response duration was 8.3 months. Median survival was 5.5 months. Four patients died secondary to chemotherapy toxicities. Those were GI perforation in one, bronchopneumonia in one, acute renal failure in one and one patient died at home 3 weeks following the third cycle. The above regimen demonstrates excessive toxicity and moderate activity. It cannot be recommended in its present format. Novel anti-cancer agents need to explored.

Acute Kidney Injury↗

Intraoperative sponge 5-fluorouracil to reduce postoperative scarring in strabismus surgery.

INTRODUCTION: To determine whether 5-fluorouracil is effective in reducing scarring after strabismus surgery we used rectus muscle surgery in experimental animals to compare a single intraoperative dose of 5-fluorouracil with mitomycin C and to compare results in similarly treated controls not receiving these antimetabolites. METHODS: Muscle resections were performed on eight rabbits (16 eyes). Four eyes had 5-fluorouracil (50 mg/ml), and four eyes received mitomycin C (0.2 mg/ml), each of which was applied during surgery on an ophthalmic sponge for 5 minutes. Eight eyes served as controls. Six weeks after surgery conjunctival vascularity, muscle length-tension curves, muscle disinsertion force, and the histologic degree of scarring were assessed. RESULTS: The mitomycin C-treated eyes clearly had more conjunctival avascularity and a lower disinsertion force. Both treated groups had flatter length-tension curves and less scarring on histologic examination than the control eyes. CONCLUSIONS: Antifibroproliferative therapy with intraoperative sponge 5-fluorouracil appears as effective as, and is possibly safer than, mitomycin C. It may be a useful adjunct in recurrent strabismus surgery or in other situations where a risk of excessive postoperative scarring exists.

Administration, Topical↗

Rapid determination of 5-fluorouracil in plasma using capillary electrophoresis.

A rapid, simple and sensitive capillary electrophoresis (CE) method used for the determination of 5-fluorouracil in rabbit plasma is described in the present paper. In this method, samples were simply pretreated by a solvent extraction procedure prior to injection. With a running buffer composed of 30 mM Tris-H(3)PO(4) (pH 7.0) and 5% isopropanol, 5-fluorouracil was easily separated from the external standard alpha-phenethylol as well as other substances existed in the plasma. A linearity of 5-fluorouracil was determined in the range from 0.17 to 42.50 microg/ml with a correlation coefficient of 0.999. A limit of quantitation (LOQ) corresponding to signal-to-noise ratio of 10 was obtained (LOQ=0.08 microg/ml). The method was successfully used for determining the 5-fluorouracil in real plasma samples from rabbits.

Animals↗

Kinetic insights into the role of the solvent in the polymorphism of 5-fluorouracil from molecular dynamics simulations.

We investigate the fundamental factors controlling polymorphism in 5-fluorouracil by performing molecular dynamics simulations of solutions of the compound in water, nitromethane, and wet nitromethane. Analysis of the effect of solvent on the initial aggregation of 5-fluorouracil molecules shows that the strong binding of water to the 5-fluorouracil molecule hinders the formation of the doubly hydrogen-bonded dimer and, by default, promotes close hydrophobic F...F interactions that are a feature of the unusual (Z' = 4) structure of form I. In contrast, doubly hydrogen-bonded dimers are observed to form readily in solution in dry nitromethane, consistent with the crystallization of the doubly hydrogen-bonded ribbon structure of form II from this solvent. When nitromethane is doped with water, the water forms hydrogen bonds to the solute, interfering with the formation of the doubly hydrogen-bonded dimers, which is consistent with the crystallization of form I from this hygroscopic solvent when it is not dried. Overall, the molecular dynamics simulations provide an atomistic picture of how solvent-solute interactions can significantly affect the initial association of 5-fluorouracil molecules to the extent that they determine the polymorphic outcome of the crystallization.

Antimetabolites, Antineoplastic↗

The addition of low-dose leucovorin to the combination of 5-fluorouracil- levamisole does not improve survival in the adjuvant treatment of Dukes' C colon cancer. IKN Colon Trial Group.

PURPOSE: To assess the effect of the addition of leucovorin to the combination of 5-fluorouracil (5-FU)-levamisole on recurrence risk and overall survival in patients after a resection with curative intent of a Dukes' C colon cancer. PATIENTS AND METHODS: Five hundred patients with Dukes' C colon cancer were randomly assigned to adjuvant treatment for one year with 5-fluorouracil (450 mg/m2 i.v. weekly) and levamisole (150 mg p.o. every two weeks), the C-group or with leucovorin (20 mg/m2 i.v.), 5-fluorouracil and levamisole, the L-group. The median follow-up for patients still alive is 36 months. Four patients were ineligible because of advanced disease at the time of randomisation. RESULTS: Sixty percent of the patients have completed all courses of chemotherapy. Of the remaining 40% of the patients who did not complete one-year treatment with chemotherapy, 46% discontinued because of toxic and/or emotional reasons. They were equally divided over both treatment arms. The addition of leucovorin increased toxicity (especially mucositis and conjunctivitis) without a significant increase in treatment withdrawal. Five-year disease-free interval (C-group: 49%, L-group: 46%; log-rank test, P = 0.86) and overall survival (C-group: 55%, L-group: 59%, log-rank test: P = 0.96) were very similar in both treatment arms. CONCLUSIONS: The addition of low dose leucovorin to the combination of 5-fluorouracil and levamisole in a 12-month adjuvant therapy for curatively resected Dukes' C colon cancer patients does not improve disease-free interval nor overall survival. The addition of leucovorin to the combination of 5-FU levamisole increases toxicity. Therefore leucovorin 5-FU levamisole is not recommended in a 12 months adjuvant regime of Dukes' C colon cancer.

Adenocarcinoma↗

Toxic effects of subconjunctival 5-fluorouracil and mitomycin C on ciliary body of rats.

PURPOSE: The effects of subconjunctival injection of mitomycin C and different concentrations of 5-fluorouracil on the epithelium of the ciliary body of twenty Sprague Dawley SD rats was studied. METHODS: Twenty rats were divided into four treatment groups. The first three groups received 0.2 ml of 5, 10, and 30 mg of 5-fluorouracil subconjunctivally respectively, and the fourth group 0.2 ml of 0.4 mg/ml mitomycin C subconjunctivally. The right eye received 0.2 ml of the antimetabolite, while the left eye was injected with 0.2 ml of saline subconjunctivally, as a control. The eyes were examined histologically, in a masked fashion, by light and by transmission electron microscopy. In each treatment group, two eyes were examined after one week, and three eyes were examined one month after the subconjunctival injection. RESULTS: Electron microscopy revealed toxic effects in the epithelium of the ciliary body of all treatment groups. The 5-fluorouracil group revealed focal mitochondrial edema, enlargement of intercellular spaces, and dilatation of intracellular spaces. The mitomycin C group showed pyknotic nuclei, enlargement of intercellular spaces, and irregular flattened epithelial cells. The severity of changes correlated with concentration and length of exposure. No pathology was found by light microscopy in all groups. CONCLUSIONS: This study demonstrates that subconjunctival antimetabolites mitomycin C and 5-fluorouracil can penetrate the sclera and exert toxic effects on the epithelium of the ciliary body, even in low doses. These changes were only apparent by electron microscopy and were still present one month after the injection. These findings may contribute to the theory that the application of antimetabolites during or after surgery has a direct effect on the epithelium of the ciliary body, besides its known effect on the conjunctiva. Further studies are needed to evaluate its effect on intraocular pressure.

Animals↗

A less toxic regimen of 5-fluorouracil and high-dose folinic acid for advanced gastrointestinal adenocarcinomas.

The combination of high-dose folinic acid with 5-fluorouracil has shown improved response rates in several trials in advanced colorectal carcinoma. This however is at the expense of increased toxicity: regimens using weekly bolus injections produce diarrhoea in most patients and occasional toxic deaths from this, whilst those using daily injections for one week in four report both diarrhoea and severe oral mucositis. Both types of regimen have significant rates of myelosuppression. A recent report described a different schedule of 5-fluorouracil and folinic acid, which appeared better tolerated but equally active (De Gramont et al., 1988). Here we report results using the same programme, in 64 patients with advanced adenocarcinomas. (Forty three colorectal, ten gastric, six pancreatic and five of unknown primary.) Patients received 200 mg m-2 folinic acid by infusion over 2 h followed by an IV bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 400 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for a total of six to 12 courses depending upon the response. The overall response rate was 26% in 62 evaluable patients. No toxicity greater than WHO Grade II occurred. Diarrhoea and mucositis did occur in around 10% of treatments but were not troublesome. No febrile neutropenic episodes were seen. Despite previous reports which described only modest activity for this combination against stomach cancers, this regimen demonstrates low toxicity but retains good activity in the palliative treatment of both gastric and colonic adenocarcinomas.

Adenocarcinoma↗

Weekly doxorubicin and continuous infusional 5-fluorouracil for advanced breast cancer.

Drug scheduling alterations can improve the therapeutic index of both 5-fluorouracil and anthracyclines. We investigated a regimen of weekly doxorubicin and continuous infusional 5-fluorouracil (AcF) in loco-regionally recurrent and metastatic breast cancer. The aims of this phase II study were to use low-dose weekly anthracyclines in a patient group where liver metastases are a frequent problem, to optimise scheduling of 5-fluorouracil using continuous infusion and to conserve alkylating agent use for late intensification in responding patients. Fifty-six patients received 5-fluorouracil 200 mg m-2 day-1 and doxorubicin 20-30 mg m-2 week-1 for at least 6 weeks. Sixty-two percent were chemonaive. Patients were evaluated for dose intensity, response, toxicity and survival. Of the assessable patients, 76% achieved UICC response criteria (20% complete response, 56% partial response). WHO grade 3+ toxicities were: alopecia, 98%; mucositis, 62%; neutropenia, 22%; and grade 3 palmar-plantar syndrome, 24%. Median survival was 13 months, with visceral metastasis conferring a significantly worse outcome (P = 0.03). Grade 3+ mucositis was more frequent with planned doxorubicin dose intensity > or = 25 mg m-2 week-1 (P = 0.04). AcF is highly active in breast cancer with acceptable toxicities and can be used before alkylating agent-based high-dose therapy.

Adult↗

Complications of 5--fluorouracil after trabeculectomy.

Trabeculectomy has a very high success rate, however, certain eyes are known to be at high risk of failure due to scarring of the conjunctival bleb. Such eyes include those with a previous failed filter, eyes with glaucoma secondary to uveitis and neovascularisation and the eyes of children and young adults. Trabeculectomy is generally accepted to have less successful results in patients of African race although good results are reported from some centres. The effectiveness of treatment with 5-fluorouracil in improving the results of trabeculectomy has been established in a number of pilot studies and clinical trials. Early studies used 100 mg of 5-fluorouracil in divided doses. Serious complications were recorded and lower dose regimes have been advised to improve the safety of the technique. Similar success in improving the chance of success to trabeculectomy has been found with doses of 40 mg with a lower incidence of side effects. We report complications associated with the use of 5-fluorouracil in a total dose of 50 mg in a group of 49 eyes undergoing trabeculectomy and postoperative 5-fluorouracil and describe the previously unreported increased incidence of thin cystic blebs in these eyes.

Adolescent↗

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: a low cost effective regimen.

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m(-2) i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m(-2) i.v. followed by 5-fluorouracil 400 mg m(-2) i.v. bolus and 600 mg m(-2) i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m(-2) i.v. bolus on day 2, every 6 weeks. Grades 3-4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1-61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.

Adult↗

Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells.

Differentiation therapy provides an alternative treatment of cancer that overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity and resistance to drugs. This new approach to cancer therapy focuses on the development of specific agents designed to selectively engage the process of terminal differentiation, leading to the elimination of tumorigenic cells and recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine acyclonucleoside-like compounds were designed and synthesized by structural modifications of 5-fluorouracil, a drug which causes considerable cell toxicity and morbidity, and we evaluated their applicability for differentiation therapy in human rhabdomyosarcoma cells. We tested the pyrimidine derivative GR-891, (RS)-1-[[3-(2-hydroxyethoxy)-1-isopropoxy]propyl]-5-fluorouracil, an active drug which shows low toxicity in vivo and releases acrolein which is an aldehyde with anti-tumour activity. Both GR-891 and 5-fluorouracil caused time- and dose-dependent growth inhibition in vitro; however, GR-891 showed no cytotoxicity at low doses (22.5 micromol l(-1) and 45 micromol l(-1)) and induced terminal myogenic differentiation in RD cells (a rhabdomyosarcoma cell line) treated for 6 days. Changes in morphological features and in protein organization indicated re-entry in the pathway of muscular maturation. Moreover, GR-891 increased adhesion capability mediated by the expression of fibronectin, and did not induce overexpression of P-glycoprotein, the mdr1 gene product, implicated in multidrug resistance. New acyclonucleoside-like compounds such as GR-891 have important potential advantages over 5-fluorouracil because of their lower toxicity and their ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our results suggest that this drug may be useful for differentiation therapy in this type of tumour.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Differential toxicity and pharmacokinetics of sodium and Tris salts of 5-fluorouracil in the rat.

1. Rats injected intraperitoneally (i.p.) with the Tris salt of 5-fluorouracil (1.44 mmol/kg) showed severe toxic symptoms and a 15% mortality. No mortality and no obvious toxicity, apart from intestinal toxicity, resulted after injection of the sodium salt at equimolar dosage. 2. The plasma pharmacokinetics of the two salts of 5-fluorouracil (1.44 mmol/kg) were different after i.p. injection: higher plasma levels were achieved and were sustained for longer after the Tris salt than after the sodium salt. 3. No differences in plasma pharmacokinetics were observed after intra-arterial (i.a.) injection of the two salts of 5-fluorouracil (6.576 mmol/kg). 4. Thus there are fundamental (and potentially important) differences between the biological properties of the sodium and Tris salts of 5-fluorouracil. These cannot be explained at present.

Animals↗

Effects of early postoperative 5-fluorouracil and ageing on the healing capacity of experimental intestinal anastomoses.

BACKGROUND: Results from a previous study suggested that advanced age does not affect early repair of experimental intestinal anastomoses. The present study aimed to establish whether anastomotic healing is impaired more easily in old animals by immediate postoperative chemotherapy. METHODS: Young adult (2-3 months) and old (27-30 months) rats underwent resection and anastomosis of both ileum and colon. Within each age group, subgroups received intraperitoneal saline or 5-fluorouracil in a dose of 15 or 20 mg per kg per day from the day of operation onwards. After 7 days, anastomotic healing was assessed by wound strength and collagen deposition in the wound area. RESULTS: No differences were found between young and old control groups. The higher dose of fluorouracil induced severe loss of strength with concomitant reduction of wound collagen, which was similar in both age groups (ileum: from 52(13) to 24(8) volume per cent in young animals and from 56(10) to 20(9) volume per cent in old animals; colon: from 58(10) to 37(18) volume per cent in young animals and from 65(5) to 30(17) volume per cent in old animals). The lower dose of fluorouracil induced a significantly greater loss of strength, measured as the bursting pressure, in the old animals (150(49) versus 201(59) mmHg in colon of young rats). CONCLUSION: In this model early anastomotic repair in older animals proceeds normally under optimal conditions, but it is more easily disturbed in the presence of fluorouracil.

Aging↗

Photodynamic therapy for actinic keratosis followed by 5-fluorouracil reaction.

BACKGROUND: Actinic or solar keratoses are the earliest form of cancerous lesions that are found in sun-exposed areas of the body. Treatment involves eliminating the lesions before they have a chance to progress. Mainstay therapies include curettage, cryosurgery, and topical 5-fluorouracil. A recently Food and Drug Administration-approved regime using photodynamic therapy has also been employed since 2000. OBJECTIVE: To inform physicians of the efficacy and potential inefficiency of this procedure, enabling the assessment of proper placement in the armamentarium. METHODS: This patient underwent photodynamic therapy. She was challenged with 5-fluorouracil 5 weeks after photodynamic treatment. RESULTS: The patient responded well to the photodynamic therapy and also to the challenge with the 5-fluorouracil. CONCLUSION: Did the photodynamic treatment really destroy lesions significantly? What is the mechanism for the response to 5-fluorouracil after such a short period between treatment modalities? If 33% of patients treated with photodynamic therapy require retreatment in 8 weeks, is this modality cost-effective, and what is its place in treating patients? How should this new treatment be implemented in practice? These questions must be seriously assessed.

Aminolevulinic Acid↗

[Cardiotoxicity of 5-fluorouracil. Clinical relevance of palliative radiochemotherapy of malignant head-neck tumors].

BACKGROUND: In the past cardiotoxicity has been increasingly reported as 5-fluorouracil is widely used as well in curative adjuvant as in palliative chemotherapy of malignant neoplasms. METHODS: We report on two cases of 5-fluorouracil-associated cardiotoxicity on palliative treatment of head and neck cancer and evaluate the importance of intensive drug monitoring. RESULTS: 5-fluorouracil-associated cardiotoxicity occurs with an incidence of 1.1-4.5%. Ischaemic cardiopathy due to vasospasms is believed to be the most common manifestation. CONCLUSIONS: Since most patients with head and neck cancer have risk factors for cardiovascular disease, 5-fluorouracil-associated cardiotoxicity should not be underestimated and patients should be monitored carefully.

Antineoplastic Combined Chemotherapy Protocols↗