Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors
Kahalalide F (KF) is a dehydroaminobutyric acid-containing peptide from marine origin with activity against several human malignant cell lines. This dose-escalating phase I clinical trial evaluated the maximum tolerated dose (MTD), and the recommended dose for further phase II studies (RD) of weekly KF given as a prolonged (3- to 24-h) intravenous (i.v.) infusion.
Eligible patients with advanced solid tumors and adequate performance status, hematologic, renal, and hepatic function were recruited into this study.
A total of 106 patients were treated with KF at four different weekly schedules: 3-h (n = 40), 24-h (n = 59), and two transitional schedules [6-h (n = 4) and 12-h (n = 3)]. For the 3-h weekly schedule, the MTD was 1,200 μg/m2 and the RD was 1,000 μg/m2. For the 24-h weekly schedule, the MTD was reached (6,650 μg/m2), but the RD could not be confirmed. Asymptomatic and reversible grade 3/4 transaminase increase was the most common dose-limiting toxicity in both schedules. Fatigue, paresthesia, pruritus, nausea, vomiting, and rash were the most common KF-related adverse events. No major deviations from linearity were detected in the pharmacokinetic (PK) profiles of both schedules, which showed a narrow distribution and short body residence. Prolonged disease stabilization (≥3 months) occurred in eight patients: two with the 3-h schedule and six with the 24-h schedule.
Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.
KeywordsKahalalide Advanced solid tumors Marine compounds Phase I clinical trials
Conflict of interest
Josep Tabernero has participated in advisory boards of Pharma Mar, and his institution has received research funding from Pharma Mar to conduct clinical trials. Cinthya Coronado, Arturo Soto Matos-Pita, Bernardo Miguel-Lillo, Martin Cullell-Young, and Jorge Luis Iglesias Dios are currently PharmaMar employees. All other authors declare no conflicts of interest.
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