Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor (EGFR) antibody h-R3: report from a phase I/II trial.
The poor prognosis of patients with high-grade glioma has led to the search for new therapeutic strategies. More than half of these tumors overexpress Epidermal Growth factor Receptor (EGFR). h-R3 is a humanized monoclonal antibody that recognize the EGFR external domain with high affinity, inhibiting tyrosine kinase activation. In order to evaluate safety, immunogenicity and preliminary efficacy of h-R3 in newly diagnosed high-grade glioma patients, we conducted a Phase I/II trial. Patients received six weekly infusions of h-R3 at the dose of 200 mg in combination with external beam radiotherapy. Twenty-nine patients (mean age, 45 years and median KPS 80) were entered into the study. Tumor types were: glioblastoma (GB) (16 patients), anaplastic astrocytoma (AA) (12 patients) and anaplastic oligodendroglioma (AO) (1 patient). All patients underwent debulking surgery or biopsy before entering the trial. The antibody was very well tolerated. No evidences of grade 3/4 adverse events were detected. None of the patients developed acneiform rash or allergic reactions. One patient developed a positive anti-idiotypic response. Objective response-rate was 37.9% (17.2% complete response, 20.7% partial response) while stable disease occurred in 41.4% of the patients. With a median follow up time of 29 months, the median survival is 22.17 months for all subjects. Median survival time (MST) is 17.47 months for GB, whereas MST is not reached for AA patients.
Ramos
Tania Crombet
TC
Center of Molecular Immunology, Havana, Cuba.
Figueredo
Javier
J
Catala
Mauricio
M
González
Sandra
S
Selva
Julio C
JC
Cruz
Tania M
TM
Toledo
Carolina
C
Silva
Sergio
S
Pestano
Yanet
Y
Ramos
Mayra
M
Leonard
Idrissa
I
Torres
Olga
O
Marinello
Patricia
P
Pérez
Rolando
R
Lage
Agustín
A
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001254:Astrocytoma / Q000628:therapy*; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D005910:Glioma / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000628:therapy*; D015609:Organotechnetium Compounds; D011379:Prognosis; D016896:Treatment Outcome
C475003:99mTc-hR3 monoclonal antibody; D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015609:Organotechnetium Compounds; D066246:ErbB Receptors