title: Reversible renal toxicity resulting from high single doses of the new radiosensitizer gadolinium texaphyrin.
abstract: Gadolinium (III) texaphyrin (Gd-Tex) (NSC 695238) is a potential radiation sensitizer that selectively localizes in tumors and is detectable by magnetic resonance imaging (MRI). In this single-dose phase I trial, reversible renal 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 radiation therapy. The Gd-Tex dose was escalated in 13 patient cohorts. Doses 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 nonoliguric renal failure at the 22.3 and 29.6 mg/kg dose levels. The injury was always transient, and responded to fluid restriction and renal diet. In all patients, transient green discoloration including urine developed at doses > or =7.1 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 excluded 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 radiation volume. We recommend that 16.7 mg/kg be used as the maximum single dose to obviate even low grade renal toxicity.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: C R
authors.initials: CR
authors.lastname: Becerra
authors.forename: R D
authors.initials: RD
authors.lastname: Toto
authors.forename: D P
authors.initials: DP
authors.lastname: Carbone
authors.forename: E P
authors.initials: EP
authors.lastname: Frenkel
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005682:Gadolinium; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000652:urine; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy; D010166:Palliative Care; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium; D005682:Gadolinium