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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.
© Copyright 2002
American
Society of Clinical Oncology
Source: http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-002108-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
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