A phase III randomised clinical trial finds that low-dose weekly administration of paclitaxel and standard dose, every two weeks administration result in equal progression-free survival for women with higher-risk early-stage breast cancer who have undergone surgery.

However, researchers found that certain side effects were more common with the every two weeks regimen, suggesting the weekly schedule may be preferable.

These findings may lead to more doctors utilizing the weekly schedule, which could also result in cost savings, as the every two weeks regimen requires additional supportive care, including growth factors (e.g., pegfilgrastim) to boost white blood cell production.

Paclitaxel is a long-standing component of breast cancer treatment. The drug is typically given to patients either weekly or every two weeks, at a higher dose. Both approaches are widely used in practice but until this study, there has not been a formal comparison of their efficacies.

“Our results suggest that either regimen will give a good outcome, but the weekly schedule seems to result in better quality of life for patients, causing less muscle and bone pain and allergic reactions,” said lead study author G. Thomas Budd, MD, a medical oncologist at the Cleveland Clinic in Cleveland, Ohio.

“The findings provide assurance that women can choose the lower-dose therapy without sacrificing their chances of survival.”

In this trial, patients with node-positive or high-risk node-negative operable breast cancer first received treatment with one of three different regimens of doxorubicin and cyclophosphamide and then received one of two different regimens of paclitaxel, in a randomised fashion.

The paclitaxel regimens studied were 1) a standard-dose treatment given every two weeks for 12 weeks with pegfilgrastim support, or 2) a low-dose weekly regimen for 12 weeks.

The results of the doxorubicin and cyclophosphamide treatment were reported at ASCO in 2011, and the results of a comparison of the two ways of giving paclitaxel were reported today.

The estimated five-year progression-free survival rates for weekly and every two weeks paclitaxel were equivalent – 82 percent and 81 percent, respectively.

The two schedules differed in the type and severity of side effects: the every two week schedule was associated with higher frequency of allergic reactions (1.4 percent vs. 0.6 percent), and muscle and bone pain (11 percent vs. 3 percent), compared to the weekly schedule.

The frequency of neurologic toxicity, a common side effect involving numbness, tingling and pain of the fingers and toes, was also higher in the every two week regimen (17 percent vs. 10 percent), but this difference may have been smaller had the patients received only four cycles of every two weeks therapy (as is current practice) rather than six. (Six cycles of every two weeks regimen was selected in this study so that patients in both arms would be on treatment for 12 weeks).

“The current trial demonstrates that weekly paclitaxel dosing and every two weeks dosing were equally effective in preventing breast cancer progression. However, weekly dosing caused less toxicity, and should ultimately be associated with lower cost due to less use of granulocyte colony stimulating factor. While some oncologists have already been using the weekly schedule for adjuvant therapy, these results will motivate many doctors, including myself, to use weekly dosing,” said Andrew D. Seidman, MD, ASCO spokesperson and breast cancer expert.

Source: ASCO