NIMOTUZUMAB , A NEW TREATMENT

OPTION IN GLIOBLASTOMA MULTIFORME

AP231 THAT HAS FAILED STANDARD
Kananathan.R,Jeyaraj Navaratnam
NCI Hospital,Nilai Negeri Sembilan, Malaysia

INTRODUCTION

Glioblastoma multiforme (GBM) carries the worst prognosis of all the gliomas, with limited treatment options such as surgery (the treatment of choice), followed by adjuvant chemoradiation.Patients with O6-
methyl-guanine-DNA methyltransferase (MGMT) methylation were shown to benefit from concomitant and adjuvant temozolomide, with significantly improved survival at 2 and 5 years. However, there are
limited therapeutic options for patients who recur or progress following temozolomide. Nimotuzumab is a novel anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb), which has
exhibited superior safety profile in several clinical settings. It is the only affinity-optimized anti-EGFR monoclonal antibody, which specifically binds to tumour cells that express moderate to high EGF receptors
(Figure 1). Emerging clinical data indicate that nimotuzumab (Figure2) could be a potential treatment option in patients diagnosed with brain tumours. Here we present a patient with GBM who failed on
temozolomide, but improved with nimotuzumabancer is caused by mutations.

Figure 1: Tissue effects of targeted EGFR signalling inhibition Figure 2:Nimotuzumab interferes only with ligand – dependent EFGR activation

CASE STUDY

History of present illness:

RHT first presented at the age of 45 on August of 2005 with a headache and was diagnosed to have a frontal lobe tumour.
status-post-surgical excision of glioma/adjuvant radiotherapy, on adjuvant temozolomide (75 mg/m2), along with 20 mg of dexamethasone daily and oxycontin 40 mg bid for pain control at the time of
presentation. However, despite standard therapy, she was bedridden and unable to move about at home.
The tumour was resected, which turned out to be astrocytoma on histopathology.
The patient underwent adjuvant radiotherapy (RT) with 54Gy/27# from September to October 2005 .
Remained well till December 2009. She presented again with headache due to the tumour recurrence, and repeat excision and histopathology revealed GBM. We conducted MGMT gene promoter test on her
brain tissue and her status was confirmed as methylation.
She was then offered concomitant temozolomide (75 mg/m2 daily during RT treatment duration) and RT.
During the course of RT, she had been admitted for raised intracranial pressure that required dexamethasone 16 mg daily. She completed 56Gy/28# of RT from January to March 2010 and was continued with
adjuvant temozolomide (150 mg/m2 daily for 5 days for total 6 cycles). During this period, she had come in and out of the hospital for raised intracranial pressure.
She was on high doses of Dexamethasone 20mg daily with Oxycontin 40mg daily . It came a stage she was bedridden and unable to move about at home .
Clinically she had progressed within a short period. EGFR expression test was conducted to evaluate the possibility of using anti-EGFR mAb such as nimotuzumab as a potential treatment option for this
patient. The EGFR expression test showed strong membrane reactivity on the tissue sample.

Management:

Patient was started on Nimotuzumab 200 mg weekly (IV) on October 2010. Remarkable improvement was evident on the second visit (next week) itself, as she was ambulatory at home and more responsive.
The dexamethasone doses were also tapered down gradually, followed by lowered oxycontin dosing. Nimotuzumab was initially given on a weekly basis for 3 months, followed by maintenance schedule of 200
mg 3-weekly. She completed 40 weeks of Nimotuzumab before her disease progressed again .
She is currently on palliative care . She has completed her 26month post diagnosis of this dreaded disease.

DISCUSSION

Despite the tumour carrying MGMT promoter methylation, the patient failed to demonstrate expected clinical efficacy from standard therapy. Continued clinical progression of the tumour prompted the cessation
of temozolomide treatment and the patient was administered with a single agent nimotuzumab in view of strong EGFR expression by the tumour. Nimotuzumab was safe as well as tolerable for the patient, which
offered significant clinical value. Nimotuzumab gives the clinicians a choice of treatment for the patients who are refractory or recurrent to current standard therapy in the management of brain tumours, with
improved quality of life and minimal side effect.

Presented at the 21st Asian Pacific Cancer Conference

10 to 12th November 2011
Dedicated to Late Dr G Selvaratnam,patients and the staff’s of NCI