A phase I single-dose trial of gadolinium texaphyrin (Gd-Tex), a tumor selective radiation sensitizer detectable by magnetic resonance imaging.

Abstract

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.

• Authors: D I Rosenthal, P Nurenberg, C R Becerra, E P Frenkel, D P Carbone, B L Lum, R Miller, J Engel, S Young, D Miles, M F Renschler
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 5 Issue 4 Pg. 739-45 (Apr 1999) ISSN: 1078-0432 [Print] United States
• PMID: 10213207 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Metalloporphyrins
• Radiation-Sensitizing Agents
• motexafin gadolinium

Topics

• Adult
• Aged
• Antineoplastic Agents (pharmacokinetics, therapeutic use, toxicity)
• Combined Modality Therapy
• Digestive System (drug effects)
• Dose-Response Relationship, Drug
• Drug Eruptions
• Female
• Hematopoiesis (drug effects)
• Humans
• Kidney (drug effects)
• Liver (drug effects)
• Magnetic Resonance Imaging
• Male
• Metalloporphyrins (pharmacokinetics, therapeutic use, toxicity)
• Middle Aged
• Neoplasms (drug therapy, radiotherapy)
• Radiation-Sensitizing Agents (pharmacokinetics, therapeutic use, toxicity)
• Tissue Distribution