) The long-term aim of this research is to improve the effectiveness of radiation therapy treatment of cancer by the development of a tumor specific radiation sensitizer. Specifically, the purpose of the current proposal is to accelerate the development and clinical application of Gd-tex (NSC 695238). The proposal will study Gd-tex in the treatment of high grade gliomas, but the information obtained will have general applicability to all tumors treated with radical radiation therapy. This drug also has the interesting property of causing signal enhancement on MRI, because of the paramagnetic gadolinium. This feature will be utilized to obtain information about the distribution, retention and chemical form of the drug in tumor. A phase I clinical trial is proposed for the development of Gd-tex for use with a standard 6 and a half week radical radiotherapy treatment course in patients with Glioblastoma Multiforme (GBM). Gd-tex is retained in tumors relative to normal tissue and has a relatively short half-life in blood. It will be given as a loading regime followed by a maintenance regime with the aim of maximizing tumor levels without build-up of drug in normal tissue. MRI scanning will be used to monitor the levels in tumor. Blood pharmacokinetics will be undertaken. GBM has been chosen because radiation therapy is still the mainstay of therapy in these patients, whose prognosis is poor. Improvements in radiation therapy are therefore vital. The use of Gd-tex as an MRI contrast agent for interactive intraoperative MRI scanning for neurosurgery for brain tumors will also be investigated. The retention of this drug in tumor renders it much more suitable for this than standard contrast agents which wash out of tumor during the course of surgery. This study will also enable direct correlation to be made between tissue levels of Gd-tex, MRI signal and tumor histology. An important correlative and scientific part of both trials will be the use of MR imaging, including relaxation and spectroscopy studies, to investigate the pharmacokinetics and pharmacology of Gd-tex in tumor. The distribution of Gd-tex will also be compared with active tumor as delineated by enhanced choline signal in MRI spectroscopy. These studies will increase the scientific understanding of the drug and aid in the design of future studies. This research has been approved in concept by the Cancer Therapy Evaluation Program.
| Ford, Judith M; Seiferheld, Wendy; Alger, Jeffrey R et al. (2007) Results of the phase I dose-escalating study of motexafin gadolinium with standard radiotherapy in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys 69:831-8 |
| Wu, Genevieve N; Ford, Judith M; Alger, Jeffry R (2006) MRI measurement of the uptake and retention of motexafin gadolinium in glioblastoma multiforme and uninvolved normal human brain. J Neurooncol 77:95-103 |
