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To the Editor: Glioblastoma multiforme (GBM) is a highly malignant brain tumor and has a median survival time of 1 year. Newcastle disease virus (NDV) vaccine has been reported to be effective in some patients with advanced cancers who had exhausted conventional cancer treatment.¹ We describe a patient with recurrent GBM who was treated with NDV vaccine and demonstrated objective tumor shrinkage and neurologic improvement.

Report of a Case.
A 14-year-old boy presented in September 1994 with a large left frontotemporal mass seen on a computed tomographic scan. The tumor was grossly debulked followed by 56 Gy of radiation to the tumor bed. Pathologic analysis revealed GBM (grade IV glioma). In March 1995, the patient began taking adjuvant tamoxifen citrate at 100 mg/d. By November 1995, magnetic resonance imaging (MRI) scan showed local recurrence of the tumor, and the patient was given 3600 mg/m² of cyclophosphamide with 1.5 mg of vincristine sulfate but after a single-course MRI scan demonstrated clear progression. Therefore, chemotherapy was changed to 500 mg/m² of carboplatin with 100 mg/m² of etoposide daily for 2 days, cycled with 100 mg/m² of cisplatin. The MRI performed in March 1996 showed continued tumor enlargement. The patient's functional and neurologic status deteriorated with increasing right-sided weakness and aphasia. He became wheelchair bound, had a Karnofsky score of 40, and received phenytoin due to frequent seizures.

In April 1996, following informed consent, NDV vaccine was initiated intravenously at 1 vial (10^7.4 electroimmunodiffusion [egg infective dose] 50 per vial) daily and was increased to 2 vials daily for 2 months, to 3 vials daily until December 1997, and then to 4 vials daily, which he currently receives. Inadvertently, he continued taking tamoxifen. The MRI scans obtained from May to November 1996 showed a borderline increase in the tumor size although the patient had an improving neurologic and functional state. The patient was monitored by MRI performed every 2 months until the end of 1997 and every 3 months after that period. However, from November 1996 to September 1998, the MRI scans have demonstrated progressive shrinkage of the tumor by approximately 95% (Figure 1).

View larger version (69K): [in this window] [in a new window] Figure. The T2-Weighted Magnetic Resonance Imaging Scans Left, Scan taken during November 1996 before the Newcastle disease virus vaccine treatment. Right, Image taken during September 1998 after the Newcastle disease virus vaccine treatment. Significant shrinkage of the tumor occurred and brain edema and mass effect were decreased.

Dexamethasone was tapered from 20 mg/d in April 1996 and was discontinued by January 1997. The patient has experienced no seizures since July 1996 and phenytoin and tamoxifen were discontinued in January 1997. The patient now receives no medication other than NDV vaccine. As of March 1999, the patient walks with mild right hemiparesis, attends public school where his grades are above average, and his Karnofsky score is 90.

Comment.
Thirty-eight viruses are thought to have antineoplastic effects in either animals or humans.² The anticancer effect of NDV was first reported in 1965³ and again in 1971.⁴ An attenuated NDV vaccine was successfully tested in patients with advanced cancer in a placebo-controlled clinical trial.⁵ Although its molecular mechanism of action is poorly understood, NDV replicates selectively in malignant tissue but not in normal tissue. Tumor regression was demonstrated in immunodeficient mice, implicating a direct virus-induced cell lysis, rather than immune effector mechanisms.⁶

Currently, the two other children with GBM treated with NDV vaccine have stable tumors shown on MRI, but they improved clinically and now have received NDV vaccine for 22 and 24 months after having rapidly progressive cancer with conventional therapy prior to receiving NDV vaccine. This agent appears to have anticancer effects and no significant toxic effects, including its lack of neurotoxic effects,^2-6 and may be a promising candidate for further evaluation in patients with malignant gliomas, particularly since the prognosis of GBM remains poor.

AUTHOR INFORMATION
Acknowledgment: The monitoring of the patient by T. Siegel, MD, F. Bokstein, MD, J. M. Gomori, MD, and A. Freeman, MD, at the Hadassah University Hospital, Jerusalem, Israel, is gratefully acknowledged.

Laszlo K. Csatary, MD
United Cancer Institute
Alexandria, Va

Tibor Bakács, MD
National Institute of Oncology
Budapest, Hungary

1. Csatary LK, Moss RW, Beuth J, et al. Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Research. 1999;19:629-634. ISI | PUBMED 2. Webb HE, Gordon-Smith CE. Viruses in the treatment of cancer. Lancet. 1970;1:1206-1208. FULL TEXT | ISI | PUBMED 3. Cassell W, Garrett RE. Newcastle disease virus as an antineoplastic agent. Cancer. 1965;18:863-868. FULL TEXT | ISI | PUBMED 4. Csatary LK. Viruses in the treatment of cancer. Lancet. 1971;2:825. ISI | PUBMED 5. Csatary LK, Eckhardt S, Bukosza I, et al. Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect Prev. 1993;17:619-627. ISI | PUBMED 6. Lorence RM, Reichard KW, Katubig BB, et al. Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J Natl Cancer Inst. 1994;86:1228-1233. FREE FULL TEXT

Edited by Margaret A. Winker, MD, Deputy Editor, and Phil B. Fontanarosa, MD, Interim Coeditor.

JAMA. 1999;281:1588-1589.