FDA: Gefitinib (Iressa) does not prolong survival

The FDA issued a statement last December urging patients who take gefitinib (Iressa) to consult their physicians, since gefitinib failed to show in a clinical trial an overall survival advantage in treating patients with lung cancer.

The trial, which compared gefitinib with placebo in patients with non-small cell lung cancer who had failed other courses of cancer therapy, showed no survival benefit from taking gefitinib.

FDA approved gefitinib on May 2, 2003, under the agency’s accelerated approval (Subpart H) program, for the treatment of patients with non-small cell lung cancer who had failed two or more courses of chemotherapy. Gefitinib was approved because the data from clinical trials showed that it caused significant shrinkage in tumors in about 10% of patients, and this was thought likely to increase patients’ overall survival time.

Under the agency’s accelerated approval program, the sponsor must study the drug further after approval to verify the expected clinical benefit. After the approval of gefitinib in 2003, AstraZeneca conducted a study in approximately 1,700 patients to determine whether the drug would in fact prolong survival in comparison to patients taking placebo. The results of this study indicate that the drug did not prolong survival.

The FDA has the authority to remove a drug from the market if a postmarketing clinical study fails to verify clinical benefit. After the FDA has evaluated the recent study results, it will determine whether gefitinib should be withdrawn from the market or if other regulatory actions are appropriate.

Alternative FDA-approved therapies that patients may use include docetaxel (Taxotere) and erlotinib (Tarceva), both of which have been shown in studies to improve survival in patients with non-small cell lung cancer whose cancer has progressed while on previous therapies.

The FDA adds warnings to bevacizumab (Avastin) label

The FDA and Genentech have notified health care professionals about revisions to the label of bevacizumab (Avastin). Bevacizumab, used in combination with intravenous 5-fluorouracil-based chemotherapy, is indicated for first-line treatment of patients with metastatic carcinoma of the colon or rectum. Arterial thromboembolic events, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina, occurred at a higher incidence in patients receiving bevacizumab in combination with chemotherapy as compared to those receiving chemotherapy alone. These events were fatal in some instances.

In randomized, active-control studies, the overall incidence of arterial thromboembolic events was increased with the use of bevacizumab in combination with chemotherapy (4.4% vs. 1.9%). The incidences of both cerebrovascular arterial events (1.9% vs. 0.5%) and cardiovascular arterial events (2.1% vs. 1.0%) were increased in patients receiving bevacizumab in combination with chemotherapy. In addition, there was a correlation between age (65 years and older) and the increase in risk of thromboembolic events. The risk of these events should be viewed in the context of bevacizumab’s ability to improve overall survival in patients with metastatic colorectal cancer.

For more information, see www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Avastin.

Computer entry cases medication errors

The United States Pharmacopeia (USP) in Rockville, MD, has reported that nearly 20% of hospital and health system medication errors reported to USP’s MEDMARXSM program in 2003 involved computerization or automation. However, facilities that have implemented computerized prescriber order entry (CPOE) reported fewer harmful errors. According to the 2003 data, automated dispensing devices (ADDs) were implicated in almost 9,000 medication error events with 1.3% of those errors leading to patient harm.

These findings are part of USP’s annual report summarizing the data collected by MEDMARX, the national medication error reporting system operated by USP. The report, MEDMARX 5th Anniversary Data Report: A Chartbook of 2003 Findings and Trends 1999-2003, analyzes 235,159 medication error records voluntarily reported by 570 hospitals and health care facilities nationwide. The report includes five-year trend analysis of records for 1999-2003, as well as a focus on technology-related errors.

Errors that result from using a computer can occur in any phase of the medication use process: prescribing, transcribing/documenting, dispensing, administering, and monitoring. According to USP’s data, most computer entry (CE) errors occurred in either the transcribing/documenting phase or dispensing phase of the medication use process. In 2003, CE errors were the fourth leading cause of medication errors according to MEDMARX data. CE errors have steadily increased and represent 11.5% of all MEDMARX records from 1999 through 2003. The data indicate that nearly three-quarters of all CE errors occur after an order is written but before the medication is administrated to the patient. Other significant findings associated with CE errors:

Performance deficit was the most frequently reported cause of error in CE. A performance deficit is a cause of error in which the health care practitioner has the required skills and knowledge to execute a task but errs nonetheless.

Distractions were the leading contributing factor, accounting for 56.5% (3,293) of errors associated with CE.

Wrong-dose errors occurred more frequently in CE records compared to overall 2003 data, indicating that there was a higher occurrence of selecting the incorrect dose when a computer entry system was involved in processing the drug order after it was written.

Americans still confident about prescription drugs

Most Americans say they’re confident about the safety of prescription drugs sold in the United States, according to an Associated Press (AP) poll.

The poll was taken after questions were raised about celecoxib (Celebrex) and more than two months after rofecoxib (Vioxx) was withdrawn from the market. But it was taken before a study raised a possible heart attack-stroke link with naproxen, which is sold over the counter as Aleve.

Just more than eight in 10 people surveyed said they have confidence in the general safety of prescription drugs in this country, the poll conducted for the AP by Ipsos-Public Affairs found. Almost that many said they have confidence in the FDA.

But many of those people admit they have some worries. Only about a third said they were "very confident" about the safety of prescription drugs in the United States and half said they were "somewhat confident."

About a fourth in the poll said they were "very confident" in the FDA’s ability to ensure the safety of prescription drugs, with about half saying they were "somewhat confident." Only one in six people who took prescription drugs of any kind in the last year, 14%, said they have asked their doctor or pharmacist to re-examine the drugs they were taking since rofecoxib was taken off the market in late September and other drugs have been questioned.

The AP-Ipsos poll of 1,002 adults was taken Dec. 17-19 and has a margin of sampling error of + 3%, slightly higher for the 773 prescription drug users polled.