Hao D, Hammond LA, Eckhardt SG, et al. A phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor. Clinical Cancer Research. 2003;9:2465-71.
This Phase I study of squalamine examined 33 patients with advanced solid tumor malignancies. Squalamine was administered as a single-agent, 5-day continuous IV infusion, repeated every 3 weeks. The principal dose-limiting toxicity of squalamine was hepatotoxicity, which involved brief, asymptomatic elevations in transaminases, and hyperbilirubinemia.
The authors concluded that the recommended dose should not exceed 500 mg/m2/day as continuous IV infusion over 5 days every 3 weeks. Compared to the (Bhargava 2001) study's results on pharmacokinetics, squalamine demonstrated dose-proportional kinetics in this study.
Herbst RS, Hammond LA, Carbone DP, et al. A Phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clinical Cancer Research. 2003;9:4108-15.
This study was conducted to determine the antitumor efficacy of squalamine in combination with carboplatin and paclitaxel. Forty-five patients with stage IIIB or stage IV non-small cell lung cancer were given a 5-day continuous infusion of squalamine with standard chemotherapy. Toxicities were limited to mild myelosuppression. Squalamine showed linear pharmacokinetics. The plasma clearance of squalamine did not change by dose level. The maximum tolerated dose (MTD) recommended was found to be 300 mg/m2/day. The pharmacokinetic profile of paclitaxel remained unchanged, and clearance of carboplatin was also unaffected by co-administration with squalamine. Significantly, among the 35 evaluable patients in the study, 12 had documented partial responses, giving an objective clinical response rate of 34%.
Researchers concluded that given the safety profile and patient survival data, squalamine at its MTD combined with chemotherapy should be studied further as potential therapy for stage IIIB or IV non-small cell lung cancer.
Emerson MV, Lauer AK. Current and emerging therapies for the treatment of age-related macular degeneration. Clinical Ophthalmology. 2008;2(2):377-388.
Forty patients with age-related macular degeneration (AMD) received 25 or 50 mg/m2 of systemic squalamine lactate each week for a period of 4 weeks. It was found to be ineffective when administered intravitreally. No patients lost vision, and 26% of patients showed improvement in vision by 3 lines.
This study was supported by Geneara Corporation, which also initiated a phase III study of squalamine lactate to treat AMD, but the study was terminated.