Clinical Cancer Research The Future of Cancer Research: Science and Patient Impact
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rosenthal, D. I.
Right arrow Articles by Renschler, M. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rosenthal, D. I.
Right arrow Articles by Renschler, M. F.
Clinical Cancer Research Vol. 5, 739-745, April 1999
© 1999 American Association for Cancer Research

Clinical Trials

A Phase I Single-Dose Trial of Gadolinium Texaphyrin (Gd-Tex), a Tumor Selective Radiation Sensitizer Detectable by Magnetic Resonance Imaging1

David I. Rosenthal2, Pamela Nurenberg, Carlos R. Becerra, Eugene P. Frenkel, David P. Carbone, Bert L. Lum, Richard Miller, Julie Engel, Stuart Young, Dale Miles and Markus F. Renschler

Department of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-4283 [D. I. R.]; Departments of Radiology [P. N.] and Internal Medicine [C. R. B., E. P. F.], University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235; Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 [D. P. C.]; Division of Oncology, Stanford University, Stanford, California 94305 [B. L. L.]; and Pharmacyclics, Inc., Sunnyvale, California 94086 [R. M., J. E., S. Y., D. M., J. F. R.]

Gadolinium Texaphyrin (Gd-Tex) is a radiation sensitizer with a novel mechanism of action that sensitizes both oxic and hypoxic cells, localizes selectively in tumors, and is detectable by magnetic resonance imaging (MRI). This Phase I single-dose trial of Gd-Tex administered concurrently with radiation therapy was carried out to determine the maximally tolerated dose (MTD), dose-limiting toxicities, pharmacokinetics, and biolocalization of Gd-Tex as determined by MRI. Adults with incurable cancers of any histology requiring radiation therapy were eligible. A single i.v. dose of Gd-Tex was followed at least 2 h later by radiation therapy. The Gd-Tex dose was escalated in cohorts of 3 to 5 patients. Thirty-eight patients (median age, 58 years; range, 35–77 years) with incurable cancers of the lung (26), cervix (3), or other solid tumors (9) received a total of 41 single administrations of Gd-Tex. The Gd-Tex dose was escalated from 0.6 to 29.6 mg/kg. Irradiated sites included the thorax, brain, pelvis, bone, soft tissue, and sites of nodal metastases. The MTD was 22.3 mg/kg, determined by reversible acute tubular necrosis as the dose-limiting toxicities. Gd-Tex selectively accumulated in primary and metastatic tumors as demonstrated by MRI. No increase in radiation toxicity to normal tissues was seen. The median half-life of Gd-Tex after single-dose administration is 7.4 h. This study demonstrates that Gd-Tex is well tolerated in doses below the MTD, and that there is selective biolocalization in tumors. The maximum recommended dose for single administrations is 16.7 mg/kg.




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
J. Ramos, M. Sirisawad, R. Miller, and L. Naumovski
Motexafin gadolinium modulates levels of phosphorylated Akt and synergizes with inhibitors of Akt phosphorylation
Mol. Cancer Ther., May 1, 2006; 5(5): 1176 - 1182.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Magda, P. Lecane, R. A. Miller, C. Lepp, D. Miles, M. Mesfin, J. E. Biaglow, V. V. Ho, D. Chawannakul, S. Nagpal, et al.
Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines
Cancer Res., May 1, 2005; 65(9): 3837 - 3845.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
D. R. Miles, J. A. Smith, S.-C. Phan, S. J. Hutcheson, M. F. Renschler, J. M. Ford, and G. W. Boswell
Population Pharmacokinetics of Motexafin Gadolinium in Adults With Brain Metastases or Glioblastoma Multiforme
J. Clin. Pharmacol., March 1, 2005; 45(3): 299 - 312.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. M. Evens, P. Lecane, D. Magda, S. Prachand, S. Singhal, J. Nelson, R. A. Miller, R. B. Gartenhaus, and L. I. Gordon
Motexafin gadolinium generates reactive oxygen species and induces apoptosis in sensitive and highly resistant multiple myeloma cells
Blood, February 1, 2005; 105(3): 1265 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. A. Meyers, J. A. Smith, A. Bezjak, M. P. Mehta, J. Liebmann, T. Illidge, I. Kunkler, J.-M. Caudrelier, P. D. Eisenberg, J. Meerwaldt, et al.
Neurocognitive Function and Progression in Patients With Brain Metastases Treated With Whole-Brain Radiation and Motexafin Gadolinium: Results of a Randomized Phase III Trial
J. Clin. Oncol., January 1, 2004; 22(1): 157 - 165.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. P. Mehta, P. Rodrigus, C.H.J. Terhaard, A. Rao, J. Suh, W. Roa, L. Souhami, A. Bezjak, M. Leibenhaut, R. Komaki, et al.
Survival and Neurologic Outcomes in a Randomized Trial of Motexafin Gadolinium and Whole-Brain Radiation Therapy in Brain Metastases
J. Clin. Oncol., July 1, 2003; 21(13): 2529 - 2536.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
L. B. Harrison, M. Chadha, R. J. Hill, K. Hu, and D. Shasha
Impact of Tumor Hypoxia and Anemia on Radiation Therapy Outcomes
Oncologist, December 1, 2002; 7(6): 492 - 508.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. P. Mehta, W. R. Shapiro, M. J. Glantz, R. A. Patchell, M. A. Weitzner, C. A. Meyers, C. J. Schultz, W. H. Roa, M. Leibenhaut, J. Ford, et al.
Lead-In Phase to Randomized Trial of Motexafin Gadolinium and Whole-Brain Radiation for Patients With Brain Metastases: Centralized Assessment of Magnetic Resonance Imaging, Neurocognitive, and Neurologic End Points
J. Clin. Oncol., August 15, 2002; 20(16): 3445 - 3453.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
O. D. Perez, G. P. Nolan, D. Magda, R. A. Miller, L. A. Herzenberg, and L. A. Herzenberg
Motexafin gadolinium (Gd-Tex) selectively induces apoptosis in HIV-1 infected CD4+ T helper cells
PNAS, February 19, 2002; 99(4): 2270 - 2274.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. A. Miller, K. W. Woodburn, Q. Fan, I. Lee, D. Miles, G. Duran, B. Sikic, and D. Magda
Motexafin Gadolinium: A Redox Active Drug That Enhances the Efficacy of Bleomycin and Doxorubicin
Clin. Cancer Res., October 1, 2001; 7(10): 3215 - 3221.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. J. Bernhard, J. B. Mitchell, D. Deen, M. Cardell, D. I. Rosenthal, and J. M. Brown
Re-Evaluating Gadolinium(III) Texaphyrin as a Radiosensitizing Agent
Cancer Res., January 1, 2000; 60(1): 86 - 91.
[Abstract] [Full Text]

Home page
 RadiologyHome page
J. Viala, D. Vanel, P. Meingan, E. Lartigau, P. Carde, and M. Renschler
Phases IB and II Multidose Trial of Gadolinium Texaphyrin, a Radiation Sensitizer Detectable at MR Imaging: Preliminary Results in Brain Metastases
Radiology, September 1, 1999; 212(3): 755 - 759.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.