Docetaxel/trastuzumab combination therapy for the treatment of breast cancer

Abstract

Trastuzumab is a humanised monoclonal antibody that targets the extra cellular domain of human epidermal growth factor receptor-2 (HER-2), which is overexpressed in approximately 20% of human breast cancers. Clinical benefit has been shown in breast cancer patients with HER-2 amplification or overexpression when trastuzumab is used alone or in combination with chemotherapy. Docetaxel is one of the most potent chemotherapy agents in the treatment of patients with metastatic and early-stage breast cancer. The rationale for combining these two drugs is based not only on preclinical synergic data, but also on expanding clinical results. This article reviews the results of trials investigating this two-drug combination, as well as the triple combinations including docetaxel and trastuzumab with platinum salts. These combinations appear to be amongst the most active therapies for the treatment of patients with HER-2-positive breast cancer in metastatic and potentially adjuvant settings.

Multimodality treatment of cancer with herceptin conjugated, thermomagnetic iron oxides and docetaxel loaded nanoparticles of biodegradable polymers

“…6), therefore higher concentration of docetaxel will be accumulated in the SK-BR-3 cells. Moreover, several clinical studies have demonstrated the synergistic interaction between docetaxel and herceptin [13,37]. For example, a randomized Phase II trial divided 186 patients into three groups: (1) one group treated with docetaxel alone; (2) one crossed over to receive trastuzumab after progressing docetaxel; and (3) one received docetaxel/trastuzumab first-line combination.…”

Inactivation of NF-κB by 3,3′-diindolylmethane contributes to increased apoptosis induced by chemotherapeutic agent in breast cancer cells

“…However, to achieve greater inhibitory effect, combination treatment with other chemopreventive agents could be a better therapeutic approach. It has been reported that Taxotere is one of the most potent chemotherapeutic agents for the treatment of patients with metastatic and early-stage breast cancer (57), and several studies have shown that histone deaceytylase inhibitor LAQ824 and genistein sensitize cancer cells to undergo apoptotic cell death induced by Taxotere (18,20,57). It is also known that the use of highdose Taxotere for patients with breast cancer leads to various levels of toxicity, thereby reducing its therapeutic benefit (54).…”

Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity

“…This strategy was justified by the apparent lack of pharmacokinetic interactions between DOX and DCT . Phase II studies showed that such a lack of pharmacokinetic interactions correlated with the apparent cardiac safety of DOX3 DCT compared with DOX3 PTX (Misset et al, 1999;Nabholtz et al, 2000). More recently, a phase III trial of DOX3 DCT versus DOX-cyclophosphamide as first-line chemotherapy for metastatic breast cancer confirmed that DOX3 DCT offered improved time to progression and objective response rates compared with DOX-cyclophosphamide while not increasing the incidence of CHF (Nabholtz et al, 2003).…”