Bone marrow depression fluorouracil

Fluorouracil Inhibits TS incorporation of FUTP into RNA resulting in alteration in RNA processing incorporation of FdUTP into DNA resulting in inhibition of DNA synthesis and function Colorectal cancer, anal cancer, breast cancer, gastroesophageal cancer, head and neck cancer, hepatocellular cancer Nausea, mucositis, diarrhea, bone marrow depression, neurotoxicity... 

Cyclophosphamide (Cytoxan and Endoxan) is used in the treatment of Hodgkin s disease, lymphosarcoma, and other lymphomas. It is employed as a secondary drug in patients with acute leukemia and in combination with doxorubicin in women with breast cancer. A drug combination effective in the treatment of breast cancer is cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP). Cyclophosphamide is also an immunosuppressive agent. The toxicity of cyclophosphamide causes alopecia, bone marrow depression, nausea and vomiting, and hemorrhagic cystitis. 

Flucytosine (Ancobon) possesses clinically useful activity against Cryptococcus neoformans, Candida species, Torulopsis glabrata, and the agents of chromomycosis. Susceptible fungi deam-inate flucytosine to 5-fluorouracil, which becomes an antimetabolite. Flucytosine, which is excreted by the kidney, should be used cautiously in the setting of renal impairment. Flucytosine is a bone marrow depressant. Flucytosine is used in combination with amphotericin B. 

Antimetabolites cause gastrointestinal toxicity including stomatitis and diarrhoea as well as bone marrow depression renal impairment potentiates the toxicity of methotrexate. Active excreHon of methotrexate by the renal tubule is blocked by salicylate, which also displaces it from plasma protein, increasing the risk of toxicity. Hepatic dysfunction potentiates the toxicity of 5-fluorouracil, since it is primarily metabolised by the liver. 

Vermes A, Guchelaar HJ, van Kuilenburg AB, Dankert J. 5-fluorocytosine-related bone-marrow depression and conversion to fluorouracil a pilot study. Fundam Clin Pharmacol 2002 16(l) 39-47. 

The hematological toxicity of fluorouracil is dose- and schedule-related (80). Leukocytes and platelets are affected, althongh the latter less so. Myelosuppression begins 4—7 days after the first dose, with recovery nsnally 14 days after the last dose (2). With continned treatment, anemia can develop in 3-4 months (81). Severe bone marrow depression causing death has been reported (82). 

The toxicity of antimetabolites is, as expected, due to their incorporation into the metabolism of normal cells, which is nearly identical to that of the malignant cells that they were designed to injure. The normal cells injured most severely are the rapidly proliferating cells of the bone marrow, the lymphoid system, and the GI epithelium. Thus, the common toxicities are bone marrow depression, nausea and vomiting, diarrhea, and mucositis. Cytarabine and pentostatin can cause conjunctivitis. Capecitabine and prolonged use of fluorouracil or cytarabine can cause cerebellar ataxia and the hand-foot syndrome, that is, palmar-plantar erythrodysesthesia or acral erythema. Pentostatin and high-dose methotrexate can cause renal toxicity. 

Oral and Gl ulcers bone marrow depression diarrhea (especially with fluorouracil and leucovorin) neurological defects, usually cerebeller cardiac arrhythmias angina pectoris alopecia hyperpigmentation palmar-plantar erythrodysesthesia conjunctivitis heart failure seizures... 

The bone marrow depressant effects of aclarubicin can be particularly severe in patients who have previously been treated with nitrosoureas or mitomycin. Aclarubicin appears not to interact with cyclophosphamide, cytarabine, enocitabine (behenoyl cy-tarabine), fluorouracil, mercaptopurine, tioguanine or vincristine. 

A depressed uptake of deoxyuridine brought about by a deficiency of vitamin B12 can be reversed as reflected by a reduction in labeled thymidine uptake by the addition of as little as 1 xg of the vitamin. Folic acid added to a concentration of 50 p.g/ml of the culture will correct abnormal results due to folate deficiency and may partially correct abnormal results due to vitamin B12 deficiency. Abnormal results may occur in bone marrow from patients with iron deficiency and from patients being treated with 5-fluorouracil (B7). 

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