Investigational New Drugs

, Volume 29, Issue 6, pp 1406–1413

Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin in patients with advanced solid tumors or lymphomas

  • Ramón Salazar
  • Ruth Plummer
  • Ana Oaknin
  • Angela Robinson
  • Beatriz Pardo
  • Arturo Soto-Matos
  • Alejandro Yovine
  • Sergio Szyldergemajn
  • Alan Hilary Calvert
PHASE I STUDIES

DOI: 10.1007/s10637-010-9488-1

Cite this article as:
Salazar, R., Plummer, R., Oaknin, A. et al. Invest New Drugs (2011) 29: 1406. doi:10.1007/s10637-010-9488-1

Summary

This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients with advanced solid tumors or lymphomas. Twenty patients were enrolled and evaluable for both safety and efficacy. The starting dose was plitidepsin 1.8 mg/m2 and carboplatin area under the curve (AUC) = 5 min*mg/ml; dose escalation proceeded based on worst toxicity in the previous cohort. The maximum tolerated dose (MTD) was plitidepsin 3.0 mg/m2 and carboplatin AUC = 5 min*mg/ml, with grade 3 transaminase increases as the most common dose-limiting toxicities (DLTs). The RD for phase II studies was plitidepsin 2.4 mg/m2 and carboplatin AUC = 5 min*mg/ml, with fatigue, myalgia and nausea as the most common drug-related adverse events (AEs). No unexpected toxicity was seen. Twelve patients (60%), ten of whom were heavily pretreated (≥2 previous chemotherapy lines) showed stable disease (SD), with a median time to progression (TTP) of 4.4 months. In conclusion, plitidepsin 2.4 mg/m2 and carboplatin AUC = 5 min*mg/ml is a safe dose for future phase II studies evaluating the use of this combination in cancer patients potentially sensitive to platinum-based therapy.

Keywords

PlitidepsinCarboplatinAdvanced solid tumorsMarine compounds

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ramón Salazar
    • 1
  • Ruth Plummer
    • 2
  • Ana Oaknin
    • 1
  • Angela Robinson
    • 2
  • Beatriz Pardo
    • 1
  • Arturo Soto-Matos
    • 3
  • Alejandro Yovine
    • 3
  • Sergio Szyldergemajn
    • 3
  • Alan Hilary Calvert
    • 2
  1. 1.Instituto Catalán de OncologíaBarcelonaSpain
  2. 2.Northern Centre for Cancer TreatmentNewcastle General HospitalNewcastle upon TyneUK
  3. 3.Pharma Mar S.A., Sociedad UnipersonalMadridSpain