FDA issues safety alerts for two cancer treatments and epoetin alfa

This week, the FDA released MedWatch alerts regarding the safety of three oncologic therapeutic agents. Chromic Phosphate P 32, erlotinib and epoetin alfa were associated with adverse events, an increased risk for cancer and even fatalities.

In a letter to health care providers, Mallinckrodt Inc. announced the addition of safety information to the prescribing information for chromic phosphate p 32 suspension (Phosphocol P 32). Two children with hemophilia developed acute lymphocytic leukemia within one year of treatment with the drug. Both patients had received intra-articular injections, an indication not approved by the FDA.

As a result of these developments, the updated packaging includes an additional warning of the risk for leukemia. The company also added an “adverse reactions statement” to include leukemia in children and radiation injury to the small bowel, cecum and bladder after administration of P32 into the peritoneal cavity.

Additional safety warnings

OSI Pharmaceuticals Inc. and Genentech Inc. issued a safety information letter for erlotinib (Tarceva) after the results of a pharmacokinetic study revealed cases of hepatic failure, hepatorenal syndrome and fatalities. Erlotinib is used in the treatment of non–small cell lung cancer and pancreatic cancer.

The study included 15 patients with advanced solid tumors and moderate hepatic impairment as defined by the Child-Pugh criteria. According to the letter, 10 patients died on treatment or within 30 days of the last dose. Eight of the 10 patients died of progressive disease, one died from hepatorenal syndrome and one from rapidly progressing liver failure.

Severe hepatic impairment was observed in six of the 10 patients who died, based on baseline total bilirubin levels of >3 times the upper limit of normal. Hepatic impairment had occurred in all patients due to hepatocellular carcinoma, cholangiocarcinoma, liver metastases or other advanced cancers with liver involvement, according to the letter.

Based on the results, the company added warnings to the product labeling for patients with hepatic impairment. The warnings section now includes dosing information, suggesting that treatment be discontinued or interrupted in patients with total bilirubin >3 times the upper limit of normal or transaminases >5 times the upper limit of normal in the setting of normal pretreatment values.

Dosing safety for epoetin alfa

Preliminary data from a clinical trial in Germany regarding the use of epoetin alfa for acute ischemic stroke were recently released to the FDA. This preliminary data revealed more deaths in the treated group, compared with placebo (16% vs. 9%) over a 90-day period after the start of the trial. Doses tested were higher than those recommended by the FDA (40,000 units per day for three days).

In the double-blind, placebo-controlled, multicenter trial, the researchers used a brand of epoetin alfa not marketed in the United States, but belonging to the same class of erythropoietin-stimulating agents approved by the FDA for the treatment of certain patients with anemia. The trial included 522 patients with ischemic stroke in the middle cerebral artery.

According to the FDA, about half of all deaths occurred within seven days of beginning treatment; about 4% of patients assigned to epoetin alfa and 1% assigned placebo died from intracranial hemorrhage.

The FDA plans to address the public with conclusions and recommendations after obtaining additional data from the trial.