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Clinical Investigations |
University of Wisconsin School of Medicine and Public Health, Madison, WI (KAB, MPM); University of Pittsburgh, Pittsburgh, PA (IFP); Mayo Clinic, Rochester, MN (JMR, MMA); Children's Hospital of Philadelphia, Philadelphia, PA (PCA); Children's National Medical Center-DC, Washington, DC (GV); Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX (SB); Investigative Drug Branch, CTEP, NCI, Bethesda, MD (PI); Children's Oncology Group – Operations Center, Arcadia, CA (TZ); Keck School of Medicine of the University of Southern California, Los Angeles, CA (MK); Children's Oncology Group, Chair's Office, Bethesda, MD (GR); USA
Address correspondence to Minesh P. Mehta, Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, University Hospital & Clinics, 600 Highland Avenue, K4/B100 Radiotherapy, Madison, WI 53792, USA (mehta{at}humonc.wisc.edu).
The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intravenous bolus 2–5 h prior to standard radiation. The starting dose was 1.7 mg/kg. After first establishing that 5 doses/week for 6 weeks was tolerable, the dose of MGd was escalated until dose-limiting toxicity was reached. Radiation therapy was administered to 54 Gy in 30 once-daily fractions. Forty-four children received MGd at doses of 1.7 to 9.2 mg/kg daily prior to radiation therapy for 6 weeks. The maximum tolerated dose was 4.4 mg/kg. The primary dose-limiting toxicities were grade 3 and 4 hypertension and elevations in serum transaminases. Median elimination half-life and clearance values were 6.6 h and 25.4 ml/kg/h, respectively. The estimated median survival was 313 days (95% confidence interval, 248–389 days). The maximum tolerated dose of MGd and the recommended phase II dose was 4.4 mg/kg when administered as a daily intravenous bolus in conjunction with 6 weeks of involved field radiation therapy for pediatric intrinsic pontine gliomas.
Key Words: motexafin gadolinium • pontine glioma • radiation therapy
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