Lack of nephrotoxicity of new oral platinum drug JM216 in lung cancer patients

Purpose: The purpose of this study was to assess renal function in patients treated with the oral platinum drug JM216 [bisacetato-ammine-dichloro-cycl ohexylamine-platinum (IV)I, since the effects of JM216 on renal function ha ve only partly been investigated using serum parameters or Cr-51-EDTA clear ance. We used a sensitive method that assessed glomerular filtration rate ( GFR), effective renal plasma flow (ERPF), and indicators of tubular and glo merular 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 exp ectancy of more than 3 months and normal liver, renal and bone marrow funct ions 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 cycle s. In six SCLC patients the dose was escalated to 140 mg/m2 per day after t he first cycle. Prior to treatment, after the first cycle and after the end of treatment renal function was assessed by I-125-sodium thalamate and I-1 31-hippurate clearances to determine acute and cumulative changes in GFR an d ERPF, respectively. Furthermore, tubular and glomerular damage were asses sed by urinary excretion of beta(2)-microglobulin, lactic dehydrogenase (LD H), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and albumin. Results: In 20 evaluable patients no significant acute impairment of renal function was observed. Median (range) GFR, ERPF and filtration fraction (F F) 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 first cycle values wer e 117 ml/min (71-189 ml/min), 418 ml/min (228-709 mil min) and 0.28 (0.21-0 .33), respectively. Also, no indications of tubular or glomerular damage we re found. In four patients renal function was evaluated at the end of treat ment tone after three cycles, one after five cycles and two after six cycle s). 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 delay ed nephrotoxicity. Conclusion: We conclude that oral JM216 shows no nephrot oxicity.