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Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium
University Hospitals Gasthuisberg, Catholic University Leuven, Herestraat 49, 3000 Leuven, Belgium
Corporació Parc Taulí, C/Parc Taulí, s/n, 08208 Sabadell (Barcelona), Spain
Parc Euromedicine, 323 rue des Apothicaires, 34298 Montpellier, France
Hospital Universitari del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain
Centre Léon Bérard, 28 Rue Laennec, F-69008, Lyon, France
Pharma Mar S.A., Av. de los Reyes, 1, PI La Mina-Norte, 28770 Colmenar Viejo, Madrid, Spain
* Author to whom correspondence should be addressed.
Received: 15 July 2009; in revised form: 28 August 2009 / Accepted: 14 September 2009 / Published: 16 September 2009
Abstract: The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.
Keywords: plitidepsin; TCC; urothelium; second-line; transitional cell carcinoma
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Dumez, H.; Gallardo, E.; Culine, S.; Galceran, J.C.; Schöffski, P.; Droz, J.P.; Extremera, S.; Szyldergemajn, S.; Fléchon, A. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium. Mar. Drugs 2009, 7, 451-463.
Dumez H, Gallardo E, Culine S, Galceran JC, Schöffski P, Droz JP, Extremera S, Szyldergemajn S, Fléchon A. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium. Marine Drugs. 2009; 7(3):451-463.
Dumez, Herlinde; Gallardo, Enrique; Culine, Stephane; Galceran, Joan C.; Schöffski, Patrick; Droz, Jean P.; Extremera, Sonia; Szyldergemajn, Sergio; Fléchon, Aude. 2009. "Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium." Mar. Drugs 7, no. 3: 451-463.