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

Lookup NU author(s): Professor Ruth Plummer, Professor Alan Calvert

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Abstract

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/m(2) 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/m(2) 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/m(2) 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 (a parts per thousand yen2 previous chemotherapy lines) showed stable disease (SD), with a median time to progression (TTP) of 4.4 months. In conclusion, plitidepsin 2.4 mg/m(2) 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.


Publication metadata

Author(s): Salazar R, Plummer R, Oaknin A, Robinson A, Pardo B, Soto-Matos A, Yovine A, Szyldergemajn S, Calvert AH

Publication type: Article

Publication status: Published

Journal: Investigational New Drugs

Year: 2011

Volume: 29

Issue: 6

Pages: 1406-1413

Print publication date: 10/07/2010

ISSN (print): 0167-6997

ISSN (electronic): 1573-0646

Publisher: Springer

URL: http://dx.doi.org/10.1007/s10637-010-9488-1

DOI: 10.1007/s10637-010-9488-1


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