Guidelines for Complications of Cancer Treatment Vol VIII Part B

Capecitabine is the prodrug for 5-FU and causes hepatotoxcity.Out of 875 patients who were evaluated for toxicity in clinicaltrials, grade 3 hyperbilirubinemia occurred in 15.2% of patientsand grade 4 occurred in 3.9%. Grade 3 or 4 hyperbilirubinemiaoccurred in 22.8% of patients with hepatic metastases atbaseline (n = 566) and 12.3% of patients without hepaticmetastases (n = 309). Administration of capecitabine shouldbe interrupted if hyperbilirubinemia of grade 2 grade 3, orgrade 4 occurs until the hyperbilirubinemia resolves ordecreases in intensity to grade 1(11).Gemcitabine is commonly associated with elevated levels oftransaminases, but this is seldom of clinical significance. Threecases of fatal cholestatic hepatotoxicity have been reportedand current recommendations are for dose reduction in patientswith an elevated serum bilirubin. An elevated bilirubin levelof greater than 1.6 mg per dL requires that the dose be startedat 800 mg per m 2 and escalated only if tolerated (12).Hepatotoxicity induced by 6-MP may occur in a variety ofsettings, especially when the dose of the drug exceeds the usualdaily dose of 2 mg per kg, and may present as eitherhepatocellular or cholestatic liver disease . Elevations ofaminotransferases and serum lactate dehydrogenase are quitecommon after high-dose MTX therapy, with an incidence ofabout 14 % (13). Liver atrophy, necrosis, cirrhosis, fattychanges, and periportal fibrosis are seen with chronic low doseas in rheumatoid arthritis and where the cumulative dose >2g. (14). For the development of toxicity, cumulative dose ismore important than duration of therapy.Antitumor Antibiotics:The antitumor antibiotics include doxorubicin, daunorubicin,idarubicin, mitoxantrone, bleomycin, mitomycin, anddactinomycin. Doxorubicin, an anthracycline antibiotic. It isextensively metabolized in the liver. Impaired liver function464