Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188 Re in adult recurrent high-grade glioma.
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.
Casacó
Angel
A
Division of Clinical Trials, Center of Molecular Immunology, Habana,Cuba. casaco@cim.sld.cu
López
Gerardo
G
García
Iván
I
Rodríguez
José Arsenio
JA
Fernández
Ramsés
R
Figueredo
Javier
J
Torres
Leonel
L
Perera
Alejandro
A
Batista
Juan
J
Leyva
René
R
Peña
Yamilé
Y
Amador
Zaida
Z
González
Addys
A
Estupiñan
Barbara
B
Coca
Marcos
M
Hernández
Abel
A
Puig
Miguel
M
Iglesias
Marbelia
M
Hernández
Astrid
A
Ramos
Mayra
M
Rodríquez
Leyanis
L
Suarez
Niurelkis
N
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000633:toxicity*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D012211:Rhenium / Q000009:adverse effects* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium