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Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma
University Hospital Leuven, Catholic University Leuven, Leuven, Belgium
Instituto Valenciano de Oncologia, Valencia, Spain
Instituto Catalan de Oncologia, Barcelona, Spain
Hospital Universitario Marques de Valdecilla, Santander, Spain
Hospital General Vall d’Hebron, Barcelona, Spain
Pharma Mar S.A., Madrid, Spain
NDDO Oncology, Amsterdam, The Netherlands
Hospital Universitario 12 de Octubre, Madrid, Spain
* Author to whom correspondence should be addressed.
Received: 15 January 2009; in revised form: 17 February 2009 / Accepted: 19 February 2009 / Published: 5 March 2009
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 (7mg/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 7mg/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
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Schöffski, P.; Guillem, V.; Garcia, M.; Rivera, F.; Tabernero, J.; Cullell, M.; Lopez-Martin, J.A.; Pollard, P.; Dumez, H.; Garcia del Muro, X.; Paz-Ares, L. 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, 57-70.
Schöffski P, Guillem V, Garcia M, Rivera F, Tabernero J, Cullell M, Lopez-Martin JA, Pollard P, Dumez H, Garcia del Muro X, Paz-Ares L. Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma. Marine Drugs. 2009; 7(1):57-70.
Schöffski, Patrick; Guillem, Vincente; Garcia, Margarita; Rivera, Fernando; Tabernero, Josep; Cullell, Martin; Lopez-Martin, Jose Antonio; Pollard, Patricia; Dumez, Herlinde; Garcia del Muro, Xavier; Paz-Ares, Luis. 2009. "Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma." Mar. Drugs 7, no. 1: 57-70.