By Stephen Smith
Globe Staff / March 3, 2008 、
In patients stricken with advanced breast cancer, the disease can rage like a wildfire, jumping from hot spot to hot spot, sparking pain and disability.
So if there's a drug that can slow the fire for a while, even if it's not ultimately doused, does that justify use of the medication? And at what cost, to the patient and to society?
Late last month, federal drug regulators gave their answer when they approved a drug called Avastin for treatment of patients with advanced breast cancer. The decision proved controversial because research showed that the patients on the drug didn't live significantly longer, even though they had more time without tumor growth than patients not on Avastin.
The ruling cast a bright - and telling - light on the complexity both of developing drugs against advanced cancer and the process of approving their use. For one, it showed that scientists have yet to unravel the riddle of why a drug can slow a tumor's assault but not extend a patient's life.
But more than anything, the approval by the US Food and Drug Administration exposed a deep divide over what's "good enough" when it comes to cancer drugs.
"Every time a person finds out that their cancer is worse, it's another punch in the stomach, it is an upsetting experience, and it's difficult for people," said Dr. Eric Winer, director of the breast oncology center at Dana-Farber Cancer Institute. "And frequently, when cancer gets worse, there are symptoms associated with it."
So, Winer said, it made perfect sense to him that Avastin should be approved for use in advanced breast cancer based on its ability to halt the progress of tumors.
To Dr. Lowell Schnipper, though, the decision was surprising.
"I think typically you want to see a survival advantage with the approval of a cancer drug - or at least I as a cancer clinician want to," said Schnipper, chief of oncology at Beth Israel Deaconess Medical Center.
Avastin works by starving tumors of the blood they need to flourish. It's part of a class of drug known as angiogenesis inhibitors pioneered by the late Dr. Judah Folkman of Children's Hospital Boston. Avastin, developed by scientists at the California biotechnology company Genentech, initially won regulatory approval for treating colon cancer and, then, lung cancer. Like any other drug, doctors could use it for other purposes, and some prescribed it for breast cancer patients.
The price is steep: about $7,700 a month. But now that the FDA has specifically approved Avastin to treat breast cancer, the company has pledged to cap the cost at $55,000 a year. With the conditional regulatory approval, insurance companies are more likely to cover Avastin for breast cancer
The FDA's acceptance of the drug hinged on a trial involving 722 breast cancer patients with advanced tumors. The study found that in patients taking Avastin with another drug, Taxol, tumors stopped growing, on average, for 11.3 months, compared to 5.8 months among patients taking Taxol alone.
more stories like thisThat's good enough for Dr. Maurie Markman, vice president for clinical research at M.D. Anderson Cancer Center in Houston.
"If the goal of any new therapy is to cure metastatic breast cancer, it is going to be a very long time - if ever - before we see it," Markman said.
Instead, he said, patients and physicians alike should view advanced breast cancer as a chronic illness, and if a drug is developed that slows its progression, "then that absolutely, in and of itself, is worthy of approval for use in this country. Period.
"And," Markman said, "I would debate anybody on that point."
But slowing tumor growth does not necessarily improve a patient's quality of life, said Dr. John Erban, director of clinical programs at the Gillette Center for Breast Cancer at Massachusetts General Hospital.
"What is a true patient benefit?" Erban said.
It would be better if researchers could definitively measure something like pain reduction or symptom improvement - but instead, they're stuck with tumor size.
The pivotal study of Avastin did not reach any conclusion about changes in quality of life. Specialists and patient advocates acknowledged that researchers need to develop better ways of charting how drugs affect the daily lives of cancer patients.
"Quality of life is a very ambiguous concept," said Dr. Robert Mass, principal medical director at Genentech. "I don't know of any cancer drug that has been approved simply on a quality of life measure."
One thing researchers knew for sure: Avastin did not significantly extend life.
"That is perplexing to a lot of people," said Winer, some of whose research is funded by Genentech. "You beat the cancer back for a while and then it grows again."
Perhaps, Schnipper said, the drug thwarted the cancer cells that were the easiest mark but missed the more resilient ones. And then the cellular survivors changed their genetic clothing just enough to become invulnerable to treatment.
作者:admin@医学,生命科学 2010-11-23 05:11