Cancer Chemotherapy and Pharmacology

, Volume 72, Issue 1, pp 75–83

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
Original Article

DOI: 10.1007/s00280-013-2170-5

Cite this article as:
Salazar, R., Cortés-Funes, H., Casado, E. et al. Cancer Chemother Pharmacol (2013) 72: 75. doi:10.1007/s00280-013-2170-5

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.

Keywords

Kahalalide Advanced solid tumors Marine compounds Phase I clinical trials 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • R. Salazar
    • 1
  • H. Cortés-Funes
    • 2
  • E. Casado
    • 3
  • B. Pardo
    • 1
  • A. López-Martín
    • 2
  • C. Cuadra
    • 1
  • J. Tabernero
    • 3
  • C. Coronado
    • 2
  • M. García
    • 1
  • A. Soto Matos-Pita
    • 4
  • B. Miguel-Lillo
    • 4
  • M. Cullell-Young
    • 4
  • J. L. Iglesias Dios
    • 4
  • L. Paz-Ares
    • 2
  1. 1.Instituto Catalán de OncologíaBarcelonaSpain
  2. 2.Hospital Universitario Doce de OctubreMadridSpain
  3. 3.Hospital Vall d’Hebron, University HospitalUniversitat Autònoma de BarcelonaBarcelonaSpain
  4. 4.Pharma Mar, S.A. Sociedad UnipersonalColmenar ViejoMadridSpain

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