Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial

J Am Soc Nephrol. 2005 Feb;16(2):452-8. doi: 10.1681/ASN.2004030225. Epub 2004 Dec 8.


The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Infusions, Intravenous
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Primary Prevention / methods
  • Probability
  • Prospective Studies
  • Reference Values
  • Risk Assessment
  • Single-Blind Method
  • Theophylline / therapeutic use*
  • Treatment Outcome


  • Theophylline
  • Cisplatin