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Clinical Investigations |
1 Hospital of the University of Pennsylvania, Philadelphia, PA
2 Henry Ford Health System, Detroit, MI
3 Wake Forest University, Comprehensive Cancer Center, Winston-Salem, NC
4 Brain Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
5 National Cancer Institute, Bethesda, MD
* To whom correspondence should be addressed. E-mail: jfisher{at}jhmi.edu.
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Abstract |
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Background: Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in adults. R115777 (Zarnestra) is an oral agent with antiproliferative effects being a potent and selective inhibitor of FTPase. This multi-center, open-label, phase II study was designed to evaluate the efficacy and safety of R115777 given after surgery and prior to radiation in patients with newly diagnosed and residual enhancing GBM.
Methods: Following surgery, an MRI confirmed the presence of residual enhancing tumor. Patients on EIASDs received 600mg twice per day and those not on EIASDs received 300mg twice per day. One to three monthly cycles of R115777 was administered and radiation was initiated with progression or after three cycles. A cycle consisted of 3 weeks of continuous R115777 followed by a one week of rest prior. MRI's were done monthly. The primary endpoint was overall survival; secondary endpoints were tumor response rate and toxicity.
Results: A total of twenty-eight confirmed GBM patients entered the study. Fifteen patients (54%) were on EIASDs. The overall median time of survival is 7.7 months. There were no tumor responses. Eight patients (29%) had stable disease as the best response. The study was stopped early due to progression of the disease in 12 patients (48%). A total of 24 patients (85%) were off study before the planned treatment schedule for radiation therapy.
Conclusions: R115777 administered prior to radiation therapy in patients with newly diagnosed GBM and residual enhancing disease did not result in any measurable responses or improvement in survival. R115777 administered prior to radiation therapy is not recommended for the patients with newly diagnosed GBM.
Key Words: Glioblastoma, Radiation, Zarnestra
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