Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188 Re in adult recurrent high-grade glioma.

Abstract

Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase I clinical trial was performed to evaluate, for the first time, the toxicity and clinical effect of an intracavitary administration of a single dose of Nimotuzumab (h-R3) labeled wit (188)Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Three patients with anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of (188)Re. In patients treated with 10 mCi (n=6) transitory worsening of pre-existing neurological symptoms were observed. Two patients treated with 15 mCi (n=4) developed early severe neurological symptoms and one also developed late severe toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed stable disease during 3 months. One GBM patient had partial response for more than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete response after 3 years of treatment. Maximal tolerated dose of the radioimmunoconjugate (188)Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10 mCi of (188)Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5 % of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas.

• Authors: Angel Casacó, Gerardo López, Iván García, José Arsenio Rodríguez, Ramsés Fernández, Javier Figueredo, Leonel Torres, Alejandro Perera, Juan Batista, René Leyva, Yamilé Peña, Zaida Amador, Addys González, Barbara Estupiñan, Marcos Coca, Abel Hernández, Miguel Puig, Marbelia Iglesias, Astrid Hernández, Mayra Ramos, Leyanis Rodríquez, Niurelkis Suarez
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 7 Issue 3 Pg. 333-9 (Mar 2008) ISSN: 1555-8576 [Electronic] United States
• PMID: 18094616 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Radioisotopes
• Rhenium

Topics

• Adult
• Aged
• Antibodies, Monoclonal (pharmacokinetics, toxicity)
• Brain Neoplasms (radiotherapy)
• Clinical Trials, Phase II as Topic
• Female
• Glioma (radiotherapy)
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Radioimmunotherapy (adverse effects, methods)
• Radioisotopes (adverse effects, therapeutic use)
• Rhenium (adverse effects, therapeutic use)