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Plitidepsin: design, development, and potential place in therapy

Authors Alonso-Álvarez S, Pardal E, Sánchez-Nieto D, Navarro M, Caballero MD, Mateos MV, Martín A

Received 9 June 2016

Accepted for publication 6 October 2016

Published 19 January 2017 Volume 2017:11 Pages 253—264

DOI https://doi.org/10.2147/DDDT.S94165

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng

Sara Alonso-Álvarez,1 Emilia Pardal,2 Diego Sánchez-Nieto,3 Miguel Navarro,4 Maria Dolores Caballero,1 Maria Victoria Mateos,1 Alejandro Martín1

1Hematology Department, IBSAL-CIC-USAL, Hospital Universitario de Salamanca, Salamanca, Spain; 2Hematology Department, Hospital Virgen del Puerto, Plasencia, Spain; 3Pharmacy Department, Hospital Universitario de Salamanca, Salamanca, Spain; 4Oncology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain

Abstract: Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin®. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents. Single-agent plitidepsin has shown limited antitumor activity and a tolerable safety profile in several malignancies, such as noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma. In patients with relapsed or refractory multiple myeloma, plitidepsin activity seems to be enhanced after addition of dexamethasone while remaining well tolerated, and a Phase III trial comparing plitidepsin plus dexamethasone vs dexamethasone alone is underway. Additional studies are required to better define the role of plitidepsin in combination with other active agents in these indications. Results of plitidepsin activity in other hematological malignancies or solid tumors have been disappointing so far. Further studies analyzing its mechanisms of action and potential biomarkers will help select patients who may benefit most from this drug. In this review, we critically analyze the published studies on plitidepsin in hematological malignancies and solid tumors and discuss its current role and future perspectives in treating these malignancies. We also review its design, pharmaceutical data, and mechanism of action.

Keywords: aplidin, plitidepsin, lymphoma, myeloma, melanoma

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