Plitidepsin: design, development, and potential place in therapy.
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.
Hematology Department, IBSAL-CIC-USAL, Hospital Universitario de Salamanca, Salamanca, Spain.
Sara
S
Alonso-Álvarez
Hematology Department, Hospital Virgen del Puerto, Plasencia, Spain.
Emilia
E
Pardal
Pharmacy Department, Hospital Universitario de Salamanca, Salamanca, Spain.
Diego
D
Sánchez-Nieto
Oncology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
Miguel
M
Navarro
Hematology Department, IBSAL-CIC-USAL, Hospital Universitario de Salamanca, Salamanca, Spain.
Maria Dolores
MD
Caballero
Hematology Department, IBSAL-CIC-USAL, Hospital Universitario de Salamanca, Salamanca, Spain.
Maria Victoria
MV
Mateos
Hematology Department, IBSAL-CIC-USAL, Hospital Universitario de Salamanca, Salamanca, Spain.
Alejandro
A
Martín
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010456:Peptides, Cyclic
D000972:Antineoplastic Agents, Phytogenic; D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin
aplidin; lymphoma; melanoma; myeloma; plitidepsin