Standard early breast cancer chemo regimens comparable on survival, but not toxicity

By Gabriel Miller

NEW YORK (Reuters Health) - A large trial comparing adjuvantanthracycline- and taxane-based chemotherapy in early stagebreast cancer has shown no survival difference between the two,suggesting that any future progress in this area will come fromtherapies that target specific biologic types of breast cancer,rather than better chemotherapeutic regimens.

A third arm of the study that added gemcitabine to one ofthe regimens also showed no difference in survival.

"We have made huge progress in the adjuvant treatment ofbreast cancer but have reached a point where the addition ofother drugs used in a non-selected group of patients does notimprove outcome and increases toxicity," lead author Dr. SandraSwain, the medical director of the Washington Cancer Institutein Washington, D.C., told Reuters Health by email. "The era ofthese large nonspecific trials is over. The future is treatmentbased on the biology of the tumor with therapies directed atspecific targets."

The National Surgical Adjuvant Breast and Bowel Projectconducted the large trial, which between 2004 and 2007 enrolled4,859 women with node-positive early-stage breast cancer. Thestudy was designed to compare optimal paclitaxel- anddocetaxel-based regimens, as well as study the addition ofgemcitabine to the paclitaxel regimen. Gemcitabine hadpreviously been shown to improve outcomes in metastatic breastcancer when combined with paclitaxel.

Patients were randomly assigned to one of three regimens:

-six cycles of concurrently administered doxorubicin 50mg/m2 plus cyclophosphamide 500 mg/m2 plus docetaxel 75 mg/m2every three weeks;

-four cycles of doxorubicin 60 mg/m2 plus cyclophosphamide600 mg/m2 every two weeks followed by four cycles of paclitaxel175 mg/m2 every two weeks; or

-four cycles of doxorubicin 60 mg/m2 plus cyclophosphamide600 mg/m2 every two weeks followed by four cycles of paclitaxel175 mg/m2 plus gemcitabine 2,000 mg/m2 every two weeks.

At five years, as reported online August 12 in the Journalof Clinical Oncology, none of regimens led to a significantimprovement over the others in either disease-free or overallsurvival.

Adverse events from drug toxicities, however, weredifferent: the docetaxel regimen led to higher rates ofneutropenia and diarrhea, while the paclitaxel-based regimensproduced higher rates of sensory neuropathy.

Dr. Swain said she currently offers patients both thesix-cycle regimen of docetaxel, doxorubicin andcyclophosphamide, as well as the four-cycle, dose-dense regimenof doxorubicin and cyclophosphamide followed by paclitaxel,explaining the potential adverse effects of each.

While targeted therapies like trastuzumab have improved theoutcome for specific groups of patients such as those withelevated levels of HER2 protein in their tumors, few new optionsexist for other subgroups, Dr. Swain said.

When asked if there are currently any new options forHER2-negative early breast cancer patients - either biologicagents or new chemo regimens - Dr. Swain responded, "No,unfortunately not right now."

There is one study underway that adds everolimus to standardhormonal therapy in the adjuvant setting for patients withestrogen receptor-positive breast cancer, she added.

SOURCE: http://bit.ly/16Hkh0h

J Clin Oncol 2013.