Serious side effects more likely in new cancer drugs

NEW YORK (Reuters Health) - Many new cancer drugs may come at a price - including a higher risk of diarrhea, skin problems and high blood pressure, according to an analysis of studies used to get those medications approved.

Researchers said patients should know that serious side effects - or toxicities - with newer chemotherapy or targeted cancer drugs might be “unusual” - and they should discuss anything that doesn’t seem right with their doctor.

For their analysis, Canadian researchers used reports on 38 cancer drugs reviewed and approved by the U.S. Food and Drug Administration between 2000 and 2010. Those included medications to treat colon, breast and lung cancers.

The study showed the newer cancer drugs caused significantly more side effects, and more treatment-related deaths, than their older counterparts. “You’ve got to consider both efficacy and toxicity in the picture,” said Susan Ellenberg, who has studied drug side effects at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

She said the analysis wasn’t so surprising, and isn’t “a big alarm.”

“People are willing to accept a certain amount of excess toxicity if they think it’s going to increase the chance of having their cancer cured,” Ellenberg, who wasn’t involved in the new study, told Reuters Health. “But that’s not always true - it really depends on what the toxicity is.”

And the balance of drug benefits and side effects may be different for each individual patient, researchers said, making treatment decisions extra tough. Dr. Eitan Amir from Princess Margaret Hospital in Toronto and his colleagues consulted side effect information from new drug labels and clinical trials.

Those drugs included bevacizumab (marketed as Avastin), docetaxel (Taxotere) and sunitinib (Sutent). Studies had between 266 and 1,725 cancer patients each. The researchers found cancer patients who were randomly assigned to the newer drugs were 40 percent more likely to die from a side effect than those in comparison groups, who were typically treated with the current standard of care at the time or a drug-free placebo.

Still, less than one percent had a treatment-related death.

The number of patients who stopped taking a drug because of side effects ranged from less than one percent to seven percent. Patients in the newer treatment groups were 52 percent more likely to have a range of severe to possibly life-threatening side effects, from nerve damage to heart problems.

And ten out of 12 of the drug-related problems Amir’s team tracked were more common among people treated with the drugs under examination, according to findings published this week in the Journal of Clinical Oncology.

It may be that the original studies were too small to pick apart those effects, Amir said.


Because the FDA approved all of the newer drugs, the agency found based on clinical trials that the medications helped cancer patients more than they potentially hurt them.

“Overall, at least we can say from clinical trial patients that the benefit (of these drugs) is more than the risks,” said Dr. Shenhong Wu, a cancer doctor from Stony Brook University School of Medicine in New York, who wasn’t involved in the new study.

But patients included in large, pre-approval trials may be healthier, or younger, than most people who are expected to ultimately need the drugs - so whether a drug is worth its possible side effects will depend on each individual patient, he added.

“In the real world, patients are complicated; they have all kinds of issues. So the benefits and risks may be different,” Wu said.

Amir told Reuters Health that when patients and their doctors are discussing starting a new treatment, doctors should take into account a patient’s overall health, and not just the cancer. “I wish there were easier decisions that people with cancer had to make, but most of the drugs are toxic,” Ellenberg said.

Amir told Reuters Health the analysis should not be seen as a takedown of cancer drugs.

“These are all drugs which improve outcomes, certainly of cancer, and overall survival,” he said. “The only thing we’re trying to highlight is, it’s not as if you’re getting anything for free.”

SOURCE: Journal of Clinical Oncology, online July 16, 2012.