© 2008 THE AUTHORS JOURNAL COMPILATION © 2 0 0 8 B J U I N T E R N A T I O N A L | 1 0 1 , 1 3 4 7 – 1 3 5 5 | doi:10.1111/j.1464-410X.2008.07571.x 1347 Urological Oncology 2008 The Authors Original Article INTRAVESICAL PACLITAXEL AND CISPLATIN FOR BLADDER CANCER HADASCHIK ET AL. Paclitaxel and cisplatin as intravesical agents against non-muscle-invasive bladder cancer Boris A. Hadaschik*†, Melanie G. ter Borg*†, John Jackson‡, Richard D. Sowery*†, Alan I. So*†, Helen M. Burt‡ and Martin E. Gleave*† *The Prostate Centre at Vancouver General Hospital, †Department of Urologic Sciences, University of British Columbia, and ‡Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada Accepted for publication 29 November 2007 B.A.H. and M.G.B. contributed equally female mice and pharmacokinetic data were acquired using high-performance liquid chromatography-mass spectrometry and atomic absorption methods. To obtain efficacy data, mice with orthotopic KU7-luc tumours were administered cisplatin and/or micellar paclitaxel intravesically, and the tumour burden quantified using bioluminescence imaging. RESULTS In vitro , both cisplatin and paclitaxel potently decreased the proliferation of all cell lines tested, and in combination had an additive but not a synergistic effect. After intravesical instillation, mouse serum concentrations of cisplatin and paclitaxel were in the low microgram/millilitre range and bladder tissue concentrations achieved were 82 and 241 μ g/ g, respectively. Similar drug levels were reached using combined therapy. In vivo , all chemotherapeutic agents significantly inhibited bladder tumour growth, with the best results for combined therapy and micellar paclitaxel alone. However, there was toxicity in the combined treatment arm. CONCLUSIONS Both cisplatin and paclitaxel were absorbed at effective amounts into bladder tissues. As intravesical agents, paclitaxel had slightly stronger anticancer potency than cisplatin. Due to increased adverse events, caution should be exercised when combining both cisplatin and paclitaxel intravesically. KEYWORDS bladder cancer, cisplatin, paclitaxel, intravesical therapy, orthotopic mouse model Study Type – Aetiology (case control study) Level of Evidence 3b OBJECTIVES To investigate the effects of cisplatin and paclitaxel against human bladder cancer cells in vitro , and to obtain both pharmacokinetic and pharmacodynamic data after intravesical administration in mice. MATERIALS AND METHODS Six bladder cancer cell lines (J82, KU7, RT4, SW780, T24, UMUC3) were treated with various combined doses of both drugs and cell proliferation was evaluated 3 days later. In vivo , solutions of cisplatin and micellar paclitaxel were instilled transurethrally in INTRODUCTION Bladder cancer is the fourth most common malignancy in men and the eighth most common in women in the Western world, and continues to be a serious clinical and economic health issue [1]. At initial diagnosis, ≈ 70% of bladder cancers are not muscle-invasive [2]. However, current treatment options for superficial bladder cancer after transurethral resection are of limited efficacy. Despite intravesical immuno- or chemotherapy, up to 80% of patients with non-muscle-invasive disease will develop recurrent tumours, of which 20–30% progress to a higher stage or grade [3]. Patients with high-risk features (high tumour grade, multifocality, pathological stage T1 and associated carcinoma in situ ) progress even more frequently, and up to a third die from bladder cancer [4,5]. Systemic administration of anticancer drugs offers little therapeutic benefit for patients with superficial bladder cancer, as the urothelial layer of the