Genentech, Inc., the manufacturer of the breast cancer drug Herceptin (generic name, trastuzumab), has issued a warning to physicians that 15 women with advanced (metastatic) breast cancer have died from adverse reactions to the drug.  Genentech and the U.S. Food and Drug Administration (FDA) maintain that Herceptin is “still a very safe drug” and that 25,000 women have been treated with Herceptin since its FDA approval in September 1998.  According to a spokesperson from Genentech, 0.06% of women who received Herceptin have died from a fatal reaction to the drug (15 out of 25,000).  Herceptin is used in advanced breast cancer patients who produce too many copies of the HER2 (also written as HER-2/neu) gene. 

In addition to the 15 deaths from Herceptin, the drug has caused serious problems in 47 other women, according to a letter Genentech sent to physicians on May 4.  The rare complications of Herceptin include allergic shock and respiratory distress.  The adverse reactions were not seen in clinical trials with Herceptin prior to FDA approval.  It is common not to see any rare adverse reactions to new medications until drugs have been introduced to a larger patient population, according to Neil Cohen, a spokesperson for Genentech. 

Genentech is currently amending the labeling of Herceptin to include warnings about the newly discovered risks.  The new warning label will explain that some patients may be very sensitive to Herceptin and develop fatal reactions to the drug.  Since respiratory complications can also occur from Herceptin, physicians will need to be cautious when prescribing the drug to patients who have any lung problems. 

Dr. Patricia Keegan of the FDA Center for Biologics Evaluation and Research believes Herceptin is safe “as cancer drugs go” but wants to make sure physicians and patients are informed about the possible complications that could arise.  In nine of the 15 deaths from Herceptin, patients experienced adverse reactions within 24 hours of receiving the drug. Other women started to improve after initially developing a severe reaction to Herceptin, but later, their conditions’ worsened. 

<Herceptin is used to treat advanced breast cancer that has spread (metastatized) to other parts of the body (such as the bone, liver, or brain).  Herceptin is only prescribed for women who have a genetic mutation of the HER2 gene, which often indicates a more aggressive cancer.  The HER2 gene is found on the surface of cells and plays a key role in regulating cell growth.  However, if the HER2 is mutated, extra HER2 copies can be produced. This over-expression of HER2 may cause increased cell growth and reproduction, often resulting in more aggressive breast cancer tumors.

Herceptin works by seeking out HER2 and attaching itself to the gene on the surface of cells. By binding to the cells, Herceptin has been shown to shrink or eliminate breast cancer tumors in some patients.  It is estimated that between 25% and 30% of women with advanced breast cancer over-express the HER2 gene. 

Women currently taking Herceptin or those considering the drug therapy are encouraged to talk to their physicians about the side effects and possible adverse reactions, though the FDA and Genentech both maintain that the recently discovered fatal reaction to Herceptin is rare. 

The most common side effects of Herceptin include:

• Fever and chills
• Weakness
• Nausea or vomiting

Less common side effects of Herceptin include weakening of the heart muscle, diarrhea, loss of white blood cells, or anemia (fatigue or difficulty breathing due to a reduction of red blood cells). 

Additional Resources and References

• The May 4, 2000 Reuters report, “Genentech Warns of Small Number of Herceptin Deaths,” is available at http://biz.yahoo.com/rf/000504/l4.asp
• The May 4, 2000 MSNBC report, “Warning Issued on Breast Cancer Drug,” is available at http://www.msnbc.com/news/403525.asp
• The May 4, 2000 WebMD report by Jessie Seyfer, “Genentech Warns Doctors of 15 Deaths Linked to Breast Cancer Drug,” is available at http://my.webmd.com/content/article/1728.57233
• To learn more about Herceptin, please visit http://www.imaginis.com/breasthealth/herceptin.asp