Less is more for drug that reduces the risk of breast cancer coming back

A world first clinical trial found that a single dose of the drug zoledronate is as effective as the standard six treatments over three years for reducing the risk of recurrence for early breast cancer.
While the drug is effective, it can have debilitating side effects like aches, pains and flu-like symptoms. Up to half of patients stop their treatments early due to side effects. 

Zoledronate is given through an IV in a cancer centre and requires blood tests before it is given. Whether patients really need that many doses had not been studied until now. 

That’s where The Ottawa Hospital’s REthinking Clinical Trials (REaCT) program comes in. This research team compares existing standard cancer treatments and dosages to find out which ones are best for patients. 
In this trial, researchers randomly assigned 211 postmenopausal patients with early breast cancer to receive either one dose of zoledronate or the usual seven. 

After five years, there was no difference in cancer recurrence or survival between the two groups. These results were published in NEJM Evidence. 

When they spoke to participants three years into the study, the researchers found that the single dose of zoledronate was more convenient for patients, had fewer side effects, and was more likely to be completed than the seven doses. 

“The results for a single dose versus the standard seven doses were absolutely the same, except that patient had less side effects with the single dose,” says lead author Dr. Mark Clemons, a clinician scientist and medical oncologist at The Ottawa Hospital and professor of medicine at the University of Ottawa. “This suggests a single dose is all patients need. That means less side effects, fewer blood draws, fewer trips to hospital for treatment, and more time with their families.”

Trial participant Beth Ciavaglia was diagnosed with stage 3 breast cancer just two weeks shy of her 40th birthday. Beth was initially reluctant to join a study where she might receive less treatment. But Dr. Clemons explained how traditionally drug doses for cancer patients are often based on the maximum a patient can tolerate, not on the dose the cancer responds to. Dosing based on toxicity is not the same as dosing based on efficacy.  That resonated with Beth, who had stopped chemotherapy early due to the exhausting side effects. She decided to join the trial. 

Beth ended up being grateful she was randomized to receive one dose of zoledronate. After that dose, she woke up in the middle of the night shaking – like chills from the flu, but 10 times worse. She felt ill for three days. “I don’t know that I would have been able to complete all seven doses,” she says. 

Beth is doing well and is cancer-free. 

“Usually, patients want more treatment rather than less,” she says. “But our quality of life is important too, and that’s why patient-centered trials are so important. After surviving cancer, I was happy to suffer less and maybe help others do the same.”