Title: Diapositiva 1
1 Safety
Nimotuzumab and radiotherapy in children and
adolescents with brain stem glioma Preliminary
results from a Phase II study.
T. Crombet1, R. Cabanas2, J. Alert3, J. Valdés2,
M.C. González2, J.L. Pedrayes2, M. Ríos4, T.
Leyva4, R. Herrera4, M. Avila4 1Center of
Molecular Immunology, Clinical Immunology
Department, Havana, Cuba. 2Juan Manuel Marquez
Hospital, Oncohematology, Havana, Cuba. 3National
Institute of Oncology, Radiotherapy, Havana,
Cuba. 4Juan Manuel Marquez Hospital,
Neurosurgery, Havana, Cuba.
Background Several EGFR-targeting products have
been approved worldwide for the treatment of
different tumor localizations. Nimotuzumab is a
humanized, anti-EGFR monoclonal antibody
registered in several countries for the treatment
of advanced head and neck cancer and recurrent
glioma. A Phase II, open label clinical trial was
designed to evaluate the progression-free
survival rate at 6 months, as well as the overall
survival, of children and adolescents newly
diagnosed with brain stem gliomas treated with
nimotuzumab in combination with external beam
radiotherapy Material and methods Newly
diagnosed patients with clinical and radiological
evidence of brain stem tumor, aged between 3 - 18
years, Karnofsky gt 40, adequate renal, liver and
hematological functions, were eligible.
Nimotuzumab was administered at a dose of 150
mg/m2 weekly for 12 weeks concomitantly with
external beam radiotherapy (induction therapy).
Treatment consolidation consisted of similar
doses of nimotuzumab at a 2-week interval except
in cases of significant deterioration of the
performance status. Tumor evaluation was
performed using MRI every 12 weeks. Results Ten
patients have been enrolled in this study to
date. After completing induction therapy, 8
patients were evaluable for response, 7 patients
achieved stable disease (SD), while 1 patient
progressed. After 24 weeks, 6 patients were
evaluable and all of them showed at least disease
stabilization. At the 48 week evaluation there
were 3 evaluable patients and 2 of them had
partial responses. The most frequent adverse
event was grade 1-2 mucositis. None of the
patients developed skin rash. The study is
ongoing and updated results will be
presented. Conclusions Nimotuzumab is safe.
Preliminary results suggest efficacy of the
humanized anti-EGFR MAb in combination with
radiotherapy in children and adolescents newly
diagnosed with brain stem glioma. Trial
continuation is warranted.
Humanized Anti-EGFR MoAb Nimotuzumab
(h-R3) Humanized IgG1 Kd 10 9 M Decreases the
cell proliferation in combination with
radiotherapy. Inhibits tumor angiogenesis by the
reduction of the size of tumor vessels in
combination with radiotherapy. Induces
apoptosis Reduces the phosphorylation of ERK1/2
alone and in combination with radiotherapy Reduces
the number of microsatellites. Reduces the
number of radio-resistant CD133 positive cancer
stem cells. Induces significant regression of
well established glioma xenografts in nude mice.
Blocks EGF binding to the EGFR while allowing the
active receptor conformation
Safety
Overall Response
Description of patient population Patients with
histologically or radiologically verified
diagnosis of brain stem glioma, defined as
involvement of gt 2/3 of the pons on initial MRI,
or 2 of 3 of the following symptoms cranial
nerve deficit, long tract signs, ataxia and a
onset prior to initial diagnosis lt 6
months. Description of study treatment Patients
receive nimotuzumab (150 mg/m2 X 12 weeks) plus
RTP (50-60 Gy). Maintenance of 150 mg/m2 every 14
day until disease progression. Primary
endpoint Event free survival rate at 6
months Secondary endpoints Survival
benefit Objective response (CRPR) Duration of
response Safety Number of subjects initially
planned 40
Patients showing partial response Patient 03
(GRA) and Patient 04 (RCB)
- Conclusions
- Nimotuzumab at multiple doses was very well
tolerated in combination with radiotherapy in
children bearing brain stem glioma. - No skin rash or allergic reactions appeared.
- Preliminary results suggest efficacy of the
humanized anti-EGFR MAb in combination with
radiotherapy in children and adolescents with
newly diagnosed brain stem glioma.
Total number of all subjects randomized to date
11 Gender 4 males, 7 females Age range 3-18
years Races White 6 Black5