R E V I E W Docetaxel for the post-surgery treatment of patients with node-positive breast cancer Shubham Pant1 Meena P Chilukuri2 Bhuvaneswari Ramaswamy1 1Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University, Columbus, Ohio, USA; 2Mount Carmel Medical center, Columbus, Ohio Correspondence: Bhuvaneswari Ramaswamy Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University, Columbus, OH, USA Tel +1 614 293 6401 Fax +1 614 293 7264 Email bhuvaneswari.ramaswamy@osumc. edu Abstract: Adjuvant chemotherapy reduces risk of relapse and cancer-related mortality in early stage breast cancer. Over the last decade, taxanes (paclitaxel and docetaxel) have been incorpo- rated into various adjuvant trials and have demonstrated a signiﬁcant beneﬁt in the management of early stage breast cancer. Clinical trials using combinations of taxanes with targeted therapy have also shown considerable activity in breast cancer. This article reviews the pharmacology of docetaxel, a semi-synthetic taxane, and the clinical trials supporting its use in patients with node-positive breast cancer. Keywords: docetaxel, node-positive breast cancer, post-surgery treatment, taxanes Introduction Nodal involvement is one of the major determinants of the risk of relapse in early stage breast cancer. Adjuvant polychemotherapy improves disease-free and overall survival in early breast cancer. The addition of paclitaxel to standard anthracycline regimen resulted in further improvement in disease-free and overall survival in node-positive patients (Henderson et al 2003) leading to its approval in the management of early stage breast cancer. The key advantage of taxanes is its noninterference with the phar- macokinetics of anthracyclines and its efﬁcacy in anthracyclines-resistant disease. Docetaxel is an antineoplastic agent belonging to the taxoid family with activity against a wide range of human malignancies (Bridgewater 2004). It is a semi-synthetic agent derived from a European yew tree, Taxus baccata, and was ﬁrst identiﬁed as an alternative to paclitaxel in 1986 (Bissery et al 1995). Its chemical structure differs from paclitaxel with a hydroxyl group replacing the acetyl group at C-10 and variations at the C-13 side chain (Ringel and Horwitz 1991). These structural modiﬁcations confer enhanced solubility in aqueous solution, and clinical studies have shown that docetaxel may be active in metastatic cancers resistant to paclitaxel (Valero et al 1998; Michaud et al 2000; Verschraegen et al 2000). The current recommended dose for docetaxel is 60–100 mg/m2 given as a 1-hour infusion every 3 weeks. Although initially approved in 1996 for treatment of anthracy- cline-refractory metastatic breast cancer, docetaxel is now also approved as adjuvant therapy in the management of early, high-risk breast cancer (Ravdin et al 1995; Valero et al 1995). This review will discuss the dosing and toxicity proﬁle of docetaxel and the studies utilizing docetaxel in patients with node-positive breast cancer. Mechanism of action Docetaxel acts by binding to the beta-tubulin subunit of the microtubules, which causes stabilization of tubulin polymerization, resulting in cell cycle arrest at G2/M phase and inhibition of mitosis (Eisenhauer and Vermorken 1998). Microtubules are the backbone of the cellular skeleton that is essential for the maintenance of cell shape, intracel- lular transport, reproduction, and neurotransmission. Docetaxel has a high afﬁnity for Therapeutics and Clinical Risk Management 2008:4(2) 419–424 © 2008 Dove Medical Press Limited. All rights reserved 419