5-Fluorouracil side effects

Capecitabine is used for the treatment of colorectal and breast cancers. It is contraindicated in patients with known hypersensitivity to capecitabine or any of its components or to 5-fluorouracil and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. The use of capecitabine is restricted in patients with severe renal impairment. The drag can induce diarrhea, sometimes severe. Other side effects include anemia, hand-foot syndrome, hyperbilirubinemia, nausea, stomatitis, pyrexia, edema, constipation, dyspnea, neutropenia, back pain, and headache. Cardiotoxicity has been observed with capecitabine. A clinically important drag interaction between capecitabine and warfarin has been demonstrated. Care should be exercised when the drag is co-administered with CYP2X9 substrates. 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Other potential radiation sensitizers for cervical cancer are being explored in phase I and II trials. Paclitaxel has been combined with cisplatin in several small phase I studies. Pignata et al. (29) found that 50 mg/m2 per week of paclitaxel could be combined with weekly cisplatin (30 mg/m2) and radiation therapy with acceptable toxicity, although 10 of 18 patients in their study had grade 3-4 hematologic toxicity. Chen etal. (30) also were able to give weekly paclitaxel at a dose of 50 mg/m2 (in this case combined with 50 mg/m2 of cisplatin every three weeks) with tolerable toxicity and minimal delay in planned radiation therapy. In both studies, the dose-limiting side effect appeared to be diarrhea. It should be noted that the total dose of cisplatin delivered in these trials was lower than that used in the most successful prospective trials of cisplatin or cisplatin and fluorouracil (Table 3). 

It was previously thought that 5-FU inhibits the enzyme by classical competitive inhibition. However, it was found that 5-FU is a transition-state substrate, and it forms a covalent complex with tetrahydrofolate and the enzyme in the same way that the natural substrate does. The reaction, however, will not go to completion, since the fluoro-uridine derived from the antimetabolite remains attached to the enzyme, and the latter becomes irreversibly deactivated. Recovery can occur only through the synthesis of new enzyme. Fluorouracil is used in the treatment of breast cancer and has found limited use in some intestinal carcinomas. Unfortunately, this drug has the side effects usually associated with antimetabolites. Its prodrug, fluorocytosine (8.35, which is also an antifungal agent) is better tolerated. 

In summary, capecitabine (1), an A -carbamate pyrimidine nucleoside prodrug of cytotoxic antimetabolite 5-fluorouracil, is an FDA-approved anticancer drug that can be administered orally. This compound uses a multilayer of prodrug strategies that not only avoids side effects arising from exposure of toxic metabolites to healthy tissue but is converted to 5-fluorouracil only by enzymes preferentially expressed in many cancer cell types, thus resulting in selective delivery of the drug to tumors. Capecitabine is marketed under the trade name of Xeloda for use in the treatment of metastatic colorectal and breast cancers and metastatic breast cancer that is resistant to paclitaxel or anthracycline therapies. 

Many clinicians prescribe pyridoxine tablets or cream to manage this side-effect, however the evidence for this treatment is scarce. Severe manifestations may have to be managed by delay and/or dose modification of the patient s next cycle of chemotherapy (only the 5-fluorouracil component need be dose modified). 

Her diarrhoea has almost certainly been caused by her capecitabine treatment. Capecitabine is a prodrug of 5-fluorouracil and as such may cause similar side-effects to it. Cytotoxic drugs can cause gastrointestinal toxicity such as diarrhoea due to their effect on the rapidly dividing cells of the body, including the cells of the gastrointestinal mucosa. 

TCAs FLUOROURACIL, IMATINIB, LEFLUNOMIDE Possible t plasma concentrations of these cytotoxics Inhibition of CYP2C9-mediated metabolism. The clinical significance of this depends upon whether alternative pathways of metabolism are also inhibited by co-administered drugs Warn patients to report t side-effects and monitor blood count carefully... 

Where expectation is confined to palliation in terms of modest life prolongation of less certain quality, then the benefits and costs of treatment must be considered carefully. Preferably, palliative treatments should involve low risk of serious side effects, e.g. 5-fluorouracil-based chemotherapy for advanced colorectal cancer is well tolerated by most patients while improving survival by around 6-9 months. 

Jorda E, Galan A, BetUoch 1, Ramon D, Revert A, Torres V. Painful, red hands. A side effect of 5-fluorouracil by continuous perfusion. Int J Dermatol 1991 30(9) 653. 

Katz ME, Hansen TW. Nail plate-nail bed separation. An unusual side effect of systemic fluorouracil administration. Arch Dermatol 1979 115(7) 860-1. 

The impact of fluorine MR spectroscopy as an in vivo analytical technique was demonstrated by observations made with fluorouracil (5-FU) and has been the subject of excellent review articles [3-5, 7-10, 46, 47, 59]. 5-FU is an antimetabolite that has been used for over 45 years in the treatment of several common cancers however, significant side-effects... 

Several publications have demonstrated circadian variation in the pharmacokinetics and pharmacodynamics of 5-fluorouracil (5-FU) during constant infusions of varying rates typically infused over 5-14 days (55-57). The maximum and minimum concentrations each day based on cosinor analysis occurred at approximately 0100-0400 and 1300 hours, respectively. Dehydropyrimidine dehydrogenase (DPD) is primarily responsible for the metabolism of 5-FU and demonstrates circadian variation in activity with its maximum and minimum activity based on cosinor analysis occurring at 0100 and 1300 hours, respectively. Some patients demonstrated an inverse relationship to the plasma 5-FU concentration (55). This appeared to increase the tolerance to 5-FU side effects between OOOOh and 0400h (58, 59). 

Flucytosine generally is associated with very few side effects in patients with normal renal, GI, and hematologic function, although rash, GI discomfort, diarrhea (5% to 10%), and reversible elevations in hepatic enzymes are observed occasionally. In patients with renal dysfunction or concomitant amphotericin B therapy, leukopenia, thrombocytopenia, and (rarely) enterocolitis may occur. Although studies have suggested that little or no conversion of flucytosine to fluorouracil occurs in vitro, serum concentrations of greater than 1000 ng/mL (therapeutic for the treatment of malignancies) have been... 

Flucytosine (5-fluorocytosine), 6, is a synthetic nucleoside that is converted intracellularly to 5-fluorouracil which, consequently, interferes with protein synthesis [22]. Although this drug is indicated for disseminated cryptococcosis and disseminated candidiases, flucytosine is rarely used alone due to substantial resistance developed by many opportunistic fungal pathogens. It also has the side effect of suppressing bone marrow production which is particularly problematic in AIDS patients. Flucytosine is sometimes used in combination with amphotericin B to suppress the rapid development of resistance to the flucytosine, but the toxicity appears to increase dramatically in these circumstances [21]. 

Colin Tuma has had an intestinal adenocarcinoma resected, but there were several metastatic nodules in his liver (see Chapters 12 and 13). He completed his second course of chemotherapy with 5-fluorouracil (5-FU) and had no serious side effects. He assured his physician at his most recent checkup that, this time, he intended to comply with any instructions his physicians gave him. He ruefully commented that he wished he had returned for regular examinations after his first round of surgery for benign intestinal polyps. 

Flucytosine (5-FC) is an analogue of the natural pyrimidine cytosine that is converted to 5-fluorouracil (5-FU) in susceptible fungi. Formation of 5-FU is essential to the antimycotic effect of 5-FC 5-FU acts as a pyrimidine antimetabolite and is phosphorylated to the cytotoxic agent 5-fluorodeoxyuridine monophosphate. All of these facts are commonly emphasized in a medicinal chemistry sequence, and readers probably are aware that 5-FU is a chemotherapeutic agent that causes myelosuppression as its major toxicity. Therefore, it should not be surprising that the same side effect can be seen in patients receiving 5-FC. 

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