Phase II randomized study of Plitidepsin (Aplidin), alone or in association with L-carnitine, in patients with unresectable advanced renal cell carcinoma

Mar Drugs. 2009;7(1):57-70. doi: 10.3390/md7010057. Epub 2009 Mar 5.

Abstract

This randomized phase II study evaluated two schedules of the marine compound Plitidepsin with or without co-administration of L-carnitine in patients with renal cell carcinoma. Patients had adequate performance status and organ function. The primary endpoint was the rate of disease control (no progression) at 12 weeks (RECIST). Other endpoints included the response rate and time dependent efficacy measures. The trial also assessed the efficacy of L-carnitine to prevent Plitidepsin-related toxicity. The two regimes given as 24 hour infusion every two weeks showed hints of antitumoral activity. Disease control at 12 weeks was 15.8% in Arm A (5mg/m2, no L-carnitine) and 11,1% in Arm B (7 mg/m2 with L-carnitine). Two partial responses were observed in Arm A (19 patients), none in Arm B (20 patients). Both schedules had the same progression-free interval (2.1 months). The median overall survival was 7.0 and 7.6 months. The safety profile was similar in both arms of the trial and adverse events were mainly mild to moderate (NCI CTC version 2.0). Increasing the dose to 7 mg/m2 did not increase the treatment efficacy but the incidence of transaminase and CPK elevations and serious AEs. Coadministration of L-carnitine did not prevent muscular toxicity or CPK-elevation associated with Plitidepsin.

Keywords: Aplidin; L-carnitine; plitidepsin; renal cell carcinoma; vascular endothelial growth factor.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carnitine / administration & dosage
  • Carnitine / therapeutic use*
  • Creatine Kinase / blood
  • Depsipeptides / administration & dosage
  • Depsipeptides / adverse effects
  • Depsipeptides / therapeutic use*
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Kidney Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Peptides, Cyclic
  • Transaminases / blood

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • Peptides, Cyclic
  • Transaminases
  • Creatine Kinase
  • Carnitine
  • plitidepsin