MultiHance® in the assessment of intracranial tumors:: Results of phase II clinical studies

Purpose: To assess preliminarily the efficacy of 0.1 and 0.2 mmol/kg doses of MultiHance(R) for contrast-enhanced magnetic resonance imaging of brain tumors. Methods: Patients were imaged pre-dose using proton density (PD), T2-weighted and T1-weighted spin-echo sequences, and post-dose by repetition of the T1-weighted sequences at 0-15, 15-30, 30-45 and 45-60 min after the completion of MultiHance(R) administration. Qualitative efficacy assessments of the image sets were performed by two blinded neuroradiologists in terms of the level of diagnostic information, the type of additional information provided by post-contrast images, the best post-contrast image set in terms of diagnostic information, the radiological utility of MultiHance(R), and the detectability of brain metastases. Extensive safety and tolerability controls were performed at 3 and 24 h post-contrast. Results: Additional diagnostic information was available on MultiHance(R)-enhanced images as compared to pre-contrast images for 58.6-78.9% of patients administered 0.1 mmol/kg MultiHance(R) and 66.1-74.6% of patients administered 0.2 mmol/kg MultiHance(R). Generally, the early (0 to 30 min) post-contrast image sets were preferred, with a clear superiority at the 15-30 min post-dose time point. In a subgroup of 21 patients with brain metastases, a higher number of lesions was detected in 55.6-66.7% of the cases with 0.1 mmol/kg MultiHance(R) and in 58.3% of the cases with 0.2 mmol/kg MultiHance(R). Overall, the usefulness of MultiHance(R) was judged as good to excellent in 91.4% of the patients at both dose levels. A total of 12 of 120 patients (10%) reported 15 transient, self-resolving adverse events of mild-to-moderate intensity. No difference between doses was observed in the incidence of adverse events and no laboratory ECG or vital signs abnormalities were reported. Conclusion: MultiHance(R) is a safe and effective contrast agent for magnetic resonance assessment of brain tumors when administered intravenously at doses up to 0.2 mmol/kg.