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Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and immune adjuvant effects. A total of 47 children representing a variety of brain tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the results of the initial phase II trial, an expanded prospective phase II trial in low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based measures of tumor response. No dose-limiting toxicities have been observed. In the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs) responded, and 2 of 4 children with progressive LGG experienced stable disease for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG patients have responded. On the basis of low toxicity and the promising LGG response, poly-ICLC may be effective for childhood LGG, and the results justify biomarker studies for personalization of poly-ICLC as a single agent or adjuvant.

Rationale and Objectives: Intravascular contrast agents for magnetic resonance imaging (MRI) facilitate the quantification of tissue perfusion. The authors determined the hemodynamic tolerance of these agents., Methods: Doses of 0.05, 0.15, and 0.45 mmol/kg of the polymeric intravascular contrast agent gadolinium-DTPA-polylysine, and di-nitrobenzyl-gadolinium-DTPA, a non-polymeric intravascular contrast agent with high protein binding, and gadolinium-DTPA dimeglumine, a paramagnetic contrast agent with extracellular distribution, were injected into 18 normal male rats as a peripheral intravenous bolus. Systolic, diastolic, and mean blood pressure, left ventricular end-diastolic and developed pressure, positive rate of pressure change (+dP/dt), dP/dt, the rate-pressure product, and heart rate were recorded during a period of 20 minutes. Hemodynamic effects were established by analysis of variance for repeated measurements., Results: There was a transient increase of all blood pressure parameters and contractility for Gd-DTPA-polylysine at the dose of 0.45 mmol/kg only. Di-nitrobenzyl-Gd-DTPA increased blood pressure parameters at 0.45 mmol/kg only. At doses of 0.05 and 0.15 mmol/kg, no significant hemodynamic effects were observed., Conclusions: The authors conclude that Gd-DTPA-polylysine is hemodynamically safe at doses to 0.15 mmol/kg and acts like a plasma expander at higher doses after peripheral bolus injection in normal rats. Additional investigations are indicated to elucidate the mechanism of a nonsignificant and satiable transient hemodynamic depression after injection of 0.05 mmol/kg DNB-Gd-DTPA.

Eighteen patients with chronic progressive multiple sclerosis (MS) were treated in an open preliminary trial of the interferon inducer and immune modulator, poly ICLC. All patients produced substantial interferon levels and experienced acute side effects, including fever and transient worsening of neurologic symptoms. Of nine patients with rapid neurologic deterioration at the time of entry into the study, only three had disease progression during treatment. We conclude that poly ICLC can be administered safely to MS patients, and that a controlled trial will be necessary to determine efficacy.