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Phase II trial of motexafin gadolinium (MGd, Xcytrin®) and cranial radiation in newly diagnosed glioblastoma multiforme (GBM)
John Suh, Eric Chang, Robert Timmerman, Mark Leibenhaut, Yoshiya Yamada, Laurie E Gaspar, Aroor Rao, Jennifer Smith, See Phan, W K Alfred Yung, Minesh P Mehta, Cleveland Clinic, Cleveland, OH; M.D. Anderson Cancer Center, Houston, TX; Indiana University, Indianapolis, IN; Radiological Associates of Sacramento, Sacramento, CA; Memorial Sloan-Kettering, New York, NY; University of Colorado Health Sciences Center, Denver, CO; Kaiser Permanente, Los Angeles, CA; Pharmacyclics Inc, Sunnyvale, CA; University of Wisconsin, Madison, WI.
Pre-clinical experiments have demonstrated increased cell death in glioma cells treated with MGd and radiation compared to those treated with radiation alone. Following early promising results from a phase I trial, we recently completed a Phase II trial of MGd with radiation therapy (RT) for GBM and report preliminary results herein. Twenty five GBM patients (17 male, 8 female, age range 33-80, median age 59 years) underwent total (4) or partial (14) resection, or biopsy only (7), and subsequently received 46 Gy ( 2 Gy x 23) to the MRI T2 abnormality (with a 2 cm margin) and an additional boost dose of 14 Gy (2 Gy x 7; total dose 60 Gy) to the MR enhancing abnormality with a 2 cm margin. MGd was administered at 5 mg/kg, 2-5 hours prior to RT, daily for the first 10 fractions, and 3 x per week thereafter for a total of 22 doses. By the RTOG RPA prognostic classification system, there were 4 class III patients, 10 IV's, 10 V's and 1 VI. Eighteen patients completed all 22 doses of MGd and 22 patients completed >80%. Twenty-four patients completed the planned radiation therapy. Grade 3 or worse toxicities during the treatment period included DVT (16%), seizures (12%), pneumonia (12%), and increased GGTP (12%). Common drug related grade 1 or 2 toxicities included reversible skin (88%) and urine (72%) discoloration, vesiculobullous rash (60%), transient paresthesias (56%), and asthenia (40%). Two patients had protocol specified interruptions in treatment for transient grade 3 liver function abnormalities, the defined dose-limiting toxicity for MGd. With a median follow-up of 5.5 months, median survival has not been reached., 6 month survival is 84%.
Conclusion: Motexafin gadolinium (22 doses, 5mg/kg/d) in combination with cranial radiation (60 Gy in 30 fractions) is tolerable for GBM patients. Early follow-up shows a 6 month survival of 84%. One-year survival data will be available for presentation.
Source: ASCO