Liver cancer, drug-induced

Anti-TNF therapy can give rise to serious reactions, including anaphylaxis, sometimes fatal blood disorders, tuberculosis and other infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, rare reports of drug induced lupus and rare reports of demyelinating central nervous system disorders, which prompted the FDA to change the respective labeling of these drugs. 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

Of 54 patients with non-small-cell lung cancers treated with a combination of gemcitabine 1000 mg/m on days 1 and 8 and paclitaxel 200 mg/m on day 1, six had abnormal but significantly raised transaminases (55). The authors believed that this was drug-induced, but could not rule out underlying liver disease. 

Fatal cholestatic hver failure occurred in a 45-year-old woman with metastatic breast cancer who was given gemcitabine and carboplatin and pre-existing liver damage. After four courses of gemcitabine -I- carboplatin she developed severe decompensated cholestatic hepatitis (9). Liver biopsy showed marked cholestasis and hepatocellular injury consistent with drug-induced hepatotoxicity. 

Felbamate. Felbamate is an adjuvant anticonvulsant, containing the warning that its use is associated with a marked increase in the incidence of aplastic anemia and that patients being started on the drug should have liver function tests performed before therapy is initiated. Animal studies have revealed a statistically significant increase in hepatic cell adenomas in high dose studies (18). It is postulated that this cancer was induced by toxic by-products urethane and methyl carbamate. Felbamate is not recommended as first-line therapy and is indicated for those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia or liver failure is deemed acceptable in light of the benefits provided by its use. 

The response of the liver to any form of biliary tree obstruction induces the synthesis of ALP by hepatocytes. Some of the newly formed enzyme enters the circulation to increase the enzyme activity in serum. The elevation tends to be more notable (greater than threefold) in extrahepatic obstruction (e.g., by stone or by cancer of the head of the pancreas) than in intrahepatic obstruction and is greater the more complete the obstruction. Serum enzyme activities may reach 10 to 12 times the upper reference limit and usually return to normal on surgical removal of the obstruction. A similar increase is seen in patients with advanced primary liver cancer or widespread secondary hepatic metas-tases. Liver diseases that principally affect parenchymal cells, such as infectious hepatitis, typically show only moderately (less than threefold) increased or even normal serum ALP activities (Table 21-3). Increases may also be seen as a consequence of a reaction to drug therapy. Intestinal ALP... 

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