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

R. Salazar, H. Cortés-Funes, E. Casado, B. Pardo, A. López-Martín, C. Cuadra, J. Tabernero, C. Coronado, M. García, A. Soto Matos-Pita, B. Miguel-Lillo, M. Cullell-Young, J. L. Iglesias Dios, L. Paz-Ares

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22 Citations (Scopus)

Abstract

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/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. Conclusions: Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile. © 2013 Springer-Verlag Berlin Heidelberg.
Original languageEnglish
Pages (from-to)75-83
JournalCancer Chemotherapy and Pharmacology
Volume72
Issue number1
DOIs
Publication statusPublished - 1 Jul 2013

Keywords

  • Advanced solid tumors
  • Kahalalide
  • Marine compounds
  • Phase I clinical trials

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