Abstract
The taxanes and Herceptin have been shown to possess significant clinical activity in metastatic breast cancer. Preclinical testing of taxane/Herceptin combinations demonstrated additive and synergistic interactions with paclitaxel and docetaxel, respectively. In a pivotal clinical trial, combination of paclitaxel (3-weekly) and Herceptin was associated with an increased response rate compared with paclitaxel monotherapy (41% vs. 17%; p = 0.001). The combination therapy also significantly improved time to disease progression (6.9 vs. 2.7 months; p < 0.05). In a phase II study of weekly paclitaxel plus Herceptin in patients with normal or increased tumor HER2 levels, a response was observed in 60% of patients and the regimen was well tolerated. Responses were more frequent in patients with HER2-overexpressing tumors (83% vs. 45%). Preliminary results from a phase II study of Herceptin plus docetaxel in patients with HER2-overexpressing tumors indicate significant activity, with a response observed in 7 (44%) of 16 evaluable patients. The preliminary results of a trial of weekly docetaxel and Herceptin demonstrate a response rate of 54% in 13 evaluable patients. Additional European trials of Hercep- tin/taxane combinations as first- and second-line and adjuvant therapy are ongoing. The results of the studies to date indicate that regimens combining Herceptin with 3-weekly and weekly taxane are effective and well tolerated.
Copyright 2001 S. Karger AG, Basel
MeSH terms
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Adult
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Aged
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents, Phytogenic / administration & dosage
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Antineoplastic Agents, Phytogenic / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Biomarkers, Tumor / analysis
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Breast Neoplasms / chemistry
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / mortality
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Breast Neoplasms / pathology
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Clinical Trials, Phase II as Topic
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Clinical Trials, Phase III as Topic
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Combined Modality Therapy
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Docetaxel
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Drug Synergism
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Female
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Heart Diseases / chemically induced
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Humans
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Mice
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Mice, Nude
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Middle Aged
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Neoplasm Metastasis
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Neoplasm Proteins / analysis
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Nervous System Diseases / chemically induced
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Neutropenia / chemically induced
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Paclitaxel / administration & dosage
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Paclitaxel / adverse effects
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Paclitaxel / analogs & derivatives*
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Paclitaxel / pharmacology*
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Palliative Care
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Randomized Controlled Trials as Topic
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Receptor, ErbB-2 / analysis
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Receptor, ErbB-3 / analysis
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Salvage Therapy
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Survival Analysis
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Taxoids*
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Trastuzumab
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Treatment Outcome
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Biomarkers, Tumor
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Neoplasm Proteins
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Taxoids
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Docetaxel
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Receptor, ErbB-2
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Receptor, ErbB-3
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Trastuzumab
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Paclitaxel