SAN FRANCISCOVery 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