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

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.

• Authors: 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
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 72 Issue 1 Pg. 75-83 (Jul 2013) ISSN: 1432-0843 [Electronic] Germany
• PMID: 23645288 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Depsipeptides
• Drugs, Investigational
• kahalalide F

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy, metabolism)
• Chemical and Drug Induced Liver Injury (physiopathology, prevention & control)
• Cohort Studies
• Colorectal Neoplasms (blood, drug therapy, metabolism)
• Depsipeptides (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drugs, Investigational (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Female
• Humans
• Incidence
• Infusions, Intravenous
• Lung Neoplasms (blood, drug therapy, metabolism)
• Male
• Middle Aged
• Neoplasms (blood, drug therapy, metabolism)
• Severity of Illness Index
• Spain (epidemiology)