Phase II randomized study of Plitidepsin (Aplidin), alone or in association with L-carnitine, in patients with unresectable advanced renal cell carcinoma.
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.
University Hospital Leuven, Catholic University Leuven, Leuven, Belgium. patrick.schoffski@uz.kuleuven.be
Patrick
P
Schöffski
Vincente
V
Guillem
Margarita
M
Garcia
Fernando
F
Rivera
Josep
J
Tabernero
Martin
M
Cullell
Jose Antonio
JA
Lopez-Martin
Patricia
P
Pollard
Herlinde
H
Dumez
Xavier Garcia
XG
del Muro
Luis
L
Paz-Ares
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002331:Carnitine / Q000008:administration & dosage / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D047630:Depsipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic; D000637:Transaminases / Q000097:blood
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; D000637:Transaminases; D003402:Creatine Kinase; D002331:Carnitine; C098980:plitidepsin