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Sequential Rx effective, less toxic in metastatic breast ca

Sequential Rx effective, less toxic in metastatic breast ca

SAN ANTONIO—As first-line treatment for metastatic breast cancer in HER2-positive patients, trastuzumab (Herceptin) can be given as a single agent, followed by docetaxel (Taxotere) upon progression, without compromising time to recurrence and providing a better toxicity profile, according to a study from the Dutch Breast Cancer Trialists' Group presented at the 2007 San Antonio Breast Cancer Symposium (abstract 1077).

The study drew considerable interest at its poster presentation. "This could be because the sequential use of these agents has not been reported before," said Paul Hamberg, MD, of Erasmus Medical Center, Rotterdam. "We thought this regimen may be attractive in that it postpones docetaxel-induced toxicity."

The study included 99 patients from 22 Dutch centers. About half were hormone-receptor positive, three-quarters had received adjuvant chemotherapy or hormonal therapy, and more than one-third had received prior hormonal therapy for metastatic disease.

Patients were randomized to weekly trastuzumab, 2 mg/kg after a loading dose of 4 mg/kg, and docetaxel 100 mg/m2 every 3 weeks (combination) or to trastuzumab monotherapy, followed upon progression by single-agent docetaxel 100 mg/m2 every 3 weeks (sequential).

Although the response rate was significantly higher (P = .03) with the combination (see Table), progression-free survival was similar in both groups (P = .22), and toxicity was less with the sequential approach.

Even though progression-free survival rates were comparable, by 2 years, more patients on the combination arm had not progressed. "There is a longer 'tail' with combination therapy," Dr. Hamberg said. He added that overall survival is being analyzed and will be available soon.

There was no difference in the incidence of grade 3-4 toxicity between the two arms. All cases of neurosensory toxicity of grade 3-4, however, occurred with combination therapy (6%).


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