Reversible renal toxicity resulting from high single doses of the new radiosensitizer gadolinium texaphyrin

Gadolinium (III) texaphyrin (Gd-Tex) (NSC 695238) is a potential radiation sensitizer that selectively localizes in tumors and is detectable by magnet ic resonance imaging (MRI). In this single-dose phase I trial, reversible r enal injury was the dose-limiting toxicity. This report details that renal injury. A single intravenous dose of Gd-Tex was followed 2 hours later by r adiation therapy. The Gd-Tex dose was escalated in 13 patient cohorts, Dose s ranged from 0.6 to 29.6 mg/kg. The maximum tolerated dosage (MTD) was 22. 3 mg/kg. Three patients had grade II and one had grade III acute nonoliguri c renal failure at the 22.3 and 29.6 mg/kg dose levels. The injury was alwa ys transient, and responded to fluid restriction and renal diet. In all pat ients, transient green discoloration including urine developed at doses gre ater than or equal to7.1 mg/kg. MRI studies demonstrated image enhancement in the liver, kidneys, and in primary and metastatic tumors in all patients receiving >5.4 mg/kg. It is important that the liver and kidneys be exclud ed from the radiation volume. Gd-Tex was well tolerated at doses below the MTD. It is important that the liver and kidneys be excluded from the radiat ion volume. We recommend that 16.7 mg/kg be used as the maximum single dose to obviate even low grade renal toxicity.