Tarceva Linked to Liver Failure and Deaths

A warning was issued Tuesday about a risk of liver failure, hepatorenal syndrome and death associated with the cancer drug Tarceva. The FDA and drug makers indicate that new information will be added to the warning label about these potential Tarceva side effects, and doctors have been urged to carefully monitor their patients with liver function impairment who are given the drug.

Tarceva (generically known as erlotinib) is a cancer drug manufactured by OSI Pharmaceuticals and Genentech, Inc. It has been used by about 250,000 people worldwide and generated sales of about $866 million last year.

The FDA approved Tarceva in 2004 for treatment of non-small cell lung cancer in patients who have received at least one previous chemotherapy session that failed. In November 2005, an additional use was approved for Tarceva in combination with gemcitabine chemotherapy for treatment of pancreatic cancer.

Tarceva works by inhibiting tyrosine kinase activity in the Epidermal Growth Factor Receptor (EGFR) signaling pathway. The EGFR protein is involved in the growth of cancerous cells in non-small cell lung and pancreatic cancers.

On September 23, 2008, Genentech and OSI sent a letter to healthcare professionals about reports of liver failure, hepatorenal syndrome and two deaths among patients on Tarceva. They indicated that the warning label will be update and doctors were advised to closely monitor patients with liver impairment receiving Tarceva, especially when total billirubin is three times more than normal.

The concerns about these Tarceva side effects come from a recent study involving patients with advanced solid tumors and moderate impaired liver function. Out of 15 patients, 10 died while on the treatment or within 30 days of the last dose. One of these deaths was attributed to hepatorenal syndrome and another was caused by rapidly progressing liver failure.

Hepatorenal syndrome refers to acute renal failure that occurs due to unknown causes in patients with chronic liver disease or sudden liver failure. It is usually seen in the absence of other disease of the kidney, and has a poor prognosis unless liver function can be restored.

The new information about the risks and recommendations will be placed in the “Warnings” section of prescribing information for Tarceva.