Herceptin/Docetaxel/Platinum Effective in Advanced Breast Cancer

SAN FRANCISCO—Very high response rates were achieved in a pilot study with the combination of docetaxel (Taxotere), platinum salts, and trastuzumab (Herceptin) in advanced breast cancer. The study, under the leadership of Dennis J. Slamon, MD, of UCLA, involved 62 patients, most of whom had visceral metastases and prior adjuvant chemotherapy. More than half tested positive for HER-2/neu by fluorescence in situ hybridization (FISH).

The study evaluated the safety and efficacy of combining docetaxel, cisplatin (Platinol) or carboplatin (Paraplatin), and trastuzumab as a precursor to the phase III BCIRG 006 trial, which recently began accrual.

BCIRG 006 is randomizing women with HER-2-positive, node-positive or high-risk node-negative operable breast cancer to receive adjuvant doxorubicin (Adriamycin)/cyclophosphamide/doce-taxel with or without trastuzumab or trastuzumab, docetaxel, and either carboplatin or cisplatin.

Mark Pegram, MD, also of UCLA, presented the poster at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 193).

He said that preclinical and clinical data show substantial synergistic activity for both docetaxel and trastuzumab, and for the two agents combined with a platinum agent. Furthermore, this regimen avoids the cardiotoxicity associated with the trastuzumab/anthracycline combination, making the triplet a most attractive approach.

"The idea is to capitalize on the synergistic drug interactions for Herceptin-based therapy in breast cancer and avoid the cardiotoxicity of Adriamycin followed by Herceptin," he said.

The results of this pilot study confirmed that the combination of docetaxel, a platinum, and trastuzumab is very active and not cardiotoxic. Preliminary response data showed overall response rates of 86% with the cisplatin combination in patients who were FISH-positive, and 81% in FISH-negative patients.

In patients receiving the combination of docetaxel, carboplatin, and trastuzumab, overall responses were seen in 65% of FISH-positive patients and 41% of FISH-negative patients.

This regimen, indeed, capitalized on the synergy of these combined agents while avoiding the toxicity of doxorubicin followed by trastuzumab, Dr. Pegram said. "Cardiotoxicity could be a major concern in adjuvant therapy. Remember that stage II patients have significant survival rates, and we don’t want cardio-toxicity issues long-term," he said.