SHORT COMMUNICATION E. Fokkema á E.G.E. de Vries á S. Meijer H.J.M. Groen Lack of nephrotoxicity of new oral platinum drug JM216 in lung cancer patients Received: 5 May 1999 / Accepted: 9 August 1999 Abstract Purpose: The purpose of this study was to assess renal function in patients treated with the oral platinum drug JM216 [bisacetato-ammine-dichloro- cyclohexylamine-platinum(IV)], since the eects of JM216 on renal function have only partly been investi- gated using serum parameters or 51 Cr-EDTA clearance. We used a sensitive method that assessed glomerular ®ltration rate (GFR), eective renal plasma ¯ow (ERPF), and indicators of tubular and glomerular damage. Methods: A group of 24 patients with either non-small-cell lung cancer (NSCLC) stage IIIb/IV or small-cell lung cancer (SCLC), limited disease (LD) or extensive disease (ED), treated with JM216 were studied. All patients had no prior chemotherapy, a performance score <2, a life expectancy of more than 3 months and normal liver, renal and bone marrow functions before treatment. All patients received oral JM216 120 mg/m 2 per day for 5 consecutive days, repeated every 21 days with a maximum of six cycles. In six SCLC patients the dose was escalated to 140 mg/m 2 per day after the ®rst cycle. Prior to treatment, after the ®rst cycle and after the end of treatment renal function was assessed by 125 I- sodium thalamate and 131 I-hippurate clearances to de- termine acute and cumulative changes in GFR and ERPF, respectively. Furthermore, tubular and glomer- ular damage were assessed by urinary excretion of b 2 -microglobulin, lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and albumin. Results: In 20 evaluable patients no sig- ni®cant acute impairment of renal function was ob- served. Median (range) GFR, ERPF and ®ltration fraction (FF) before treatment were 101 ml/min (53± 164 ml/min), 417 ml/min (227±719 ml/min), and 0.25 (0.19±0.33), respectively. After the ®rst cycle values were 117 ml/min (71±189 ml/min), 418 ml/min (228±709 ml/ min) and 0.28 (0.21±0.33), respectively. Also, no indi- cations of tubular or glomerular damage were found. In four patients renal function was evaluated at the end of treatment (one after three cycles, one after ®ve cycles and two after six cycles). Median (range) GFR, ERPF and FF were 99 ml/min (74±139 ml/min), 401 ml/min (277±496 ml/min) and 0.26 (0.23±0.30), respectively, revealing no delayed nephrotoxicity. Conclusion: We conclude that oral JM216 shows no nephrotoxicity. Key words Nephrotoxicity á JM216 Introduction JM216 [bisacetato-ammine-dichloro-cyclohexamine-pla- tinum(IV)] is a novel oral platinum(IV) drug. JM216 has shown activity against several platinum-sensitive and also platinum-resistant cancer cell lines [20, 22, 23, 25]. In these cell lines JM216 can partly circumvent platinum resistance. In vivo oral JM216 shows activity compara- ble to that of intravenous cisplatin against human ovarian carcinoma xenografts, and shows even better activity against murine ADJ/PC6 plasmacytoma in mice [11]. The antitumour activity of oral JM216 is currently under investigation in phase II trials for several types of cancer. The drug has been developed in the search for new platinum drugs with a milder toxicity pro®le than cisplatin, because the use of cisplatin is often limited by its toxicities, especially nephrotoxicity [12, 13, 19]. Cis- platin is nephrotoxic probably because of its eects in changing renal perfusion and injuring tubules [7, 19]. The principal route of excretion of cisplatin is renal, by Cancer Chemother Pharmacol (2000) 45: 89±92 Ó Springer-Verlag 2000 E. Fokkema á H.J.M. Groen (&) Department of Pulmonary Diseases, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands Tel.: +31-50-3616161; Fax: +31-50-3619320 e-mail: h.j.m.groen@int.azg.nl E.G.E. de Vries Department of Medical Oncology, University Hospital Groningen, The Netherlands S. Meijer Department of Nephrology, University Hospital Groningen, The Netherlands