Harm Surfaces After New Drug Approval

Serious and sometimes life-threatening side effects often go unreported until years after cancer drugs have been approved, Canadian researchers said Monday.

Within four years of approval, five of the 12 drugs they looked at had earned a "black box warning" from the U.S. Food and Drug Administration, which approves new medications.

"It's a warning to be very careful," said Dr. Ian F. Tannock, an oncologist at the University of Toronto, who led the study. "Patients need to be informed that with a new agent there may be added risks."

Tannock's team examined so-called targeted therapies, a budding class of cancer drugs that work by interfering with specific molecules involved in tumor growth.

He said doctors had assumed the medicines would be safer than traditional chemotherapy, but that the data suggested otherwise.

"It's concerning to say the least," Dr. Thomas J. George, who was not involved in the study, told Reuters Health. Most newly approved drugs, and those now in testing, are targeted therapies.

"When we as oncologists prescribe new therapies, we have to be on the constant lookout for side effects and outcomes that aren't necessarily what the trials would have predicted," added George, of the University of Florida.

The new findings come in the wake of research showing that most trials of experimental cancer drugs report increases in at least one severe or life-threatening side effect.

But often such trials, which form the basis for FDA drug approval, are too small for rare side effects to surface, or they include only highly select patients.

That may help explain why many cancer drugs have their drug inserts updated as new side effects are reported by independent physicians, or sometimes by drugmakers conducting post-marketing studies.

The problem is that very few doctors actually look at the labels, Tannock said. Instead, they stick with the published studies that led to the drug's approval and first label.

Focusing only on drugs with updated labels, Tannock's team found that half of the 76 serious side effects described in them hadn't been on the initial label. Of potentially fatal side effects — such as blood clots, strokes, and lung problems — that number was 58 percent.

"Many of the reports that led to the warnings did not come from published studies," added Tannock, whose findings appear in the Journal of Clinical Oncology.

PhRMA, the trade group that represents drugmakers, could not provide a comment by deadline.

The new drugs include rituximab (sold as Rituxan), with four boxed warnings, and ibritumomab tiuxetan (Zevalin), with two boxed warnings, among others.

"It's concerning because we make decisions on using the drugs in patients based on the earliest reports, which are the randomized controlled trials, but it's clear that we don't have all the answers to how it is going to work in our patients," George said.

He said one solution was to create registries to monitor all patients taking the new drugs.