Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors

Purpose 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. Methods Eligible patients with advanced solid tumors and adequate performance status, hematologic, renal, and hepatic function were recruited into this study. Results 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/m 2 and the RD was 1,000 μg/m 2 . For the 24-h weekly schedule, the MTD was reached (6,650 μg/m 2 ), 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. Conclusions Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.