By Ingfei Chen
The Road After Approval
Potential harmful effects from drugs require post-market monitoring of adverse reactions
By Ingfei Chen
“Cancer Drugs Might Help Disease Return.” It was an unnerving headline that no cancer patient ever wishes to see. But there it was last March on the front page of the San Francisco Chronicle, summing up new research from the University of California, San Francisco (UCSF): Investigators had found that treating cancer with sunitinib (Sutent) or related drugs ultimately made tumors spread farther and grow more aggressively—though in mice, not in people.
The study, which was published in the March 3, 2009, Cancer Cell—alongside results from a Toronto research team that reported similar findings—raised questions about a much-heralded class of cancer-fighting medicines, called angiogenesis inhibitors. They include Sutent, bevacizumab (Avastin) and sorafenib (Nexavar). Approved by the U.S. Food and Drug Administration (FDA) in the last six years, all three drugs block angiogenesis, the sprouting of new blood vessels that supply tumors with the oxygen and nutrients they need to flourish. They are used to treat a range of advanced cancers, including those in the colon, breast, brain and kidneys.
When the drugs began to be introduced in 2004, they raised the hopes of many patients with metastatic cancer. Clinical trials show that the drugs can delay cancer progression or extend overall survival by months, buying precious time for patients in dire circumstances, although at a staggering cost of thousands of dollars a month. Furthermore, studies now under way are investigating whether these drugs might also benefit people with early-stage disease.
In this context, what do the recent findings of a potential rebound effect mean for people currently taking these drugs and for their doctors?
More than anything, perhaps this: that a drug’s possible risks and benefits are complex and constantly evolving. In other words, the initial approval of a medication is only “a snapshot of a period of time” in a long life history, says Richard Pazdur, the director of the FDA’s office of oncology drug products.
New Safety Issues
A new medicine often wins FDA approval after as few as 1,000 people have taken it in carefully controlled clinical trials, says Otis Brawley, the chief medical officer for the American Cancer Society. But once the drug reaches thousands or hundreds of thousands of patients in everyday medical practice, adverse reactions that were too rare to be detected in individual studies start cropping up. Furthermore, new laboratory studies may uncover potential problems.