Trabectedin (
Yondelis(®)) is a potent marine-derived
antineoplastic drug with high activity against various
soft tissue sarcoma (STS) subtypes as monotherapy, and in combination with
pegylated liposomal doxorubicin (
PLD) for the treatment of patients with relapsed
platinum-sensitive
ovarian cancer. This article reviews the safety and pharmacokinetic profiles of
trabectedin. Records were identified using predefined search criteria using electronic databases (e.g. PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published between 1 January 2006 and 1 April 2014 were included. The current safety and tolerability profile of
trabectedin, based on the evaluation in clinical trials of patients treated with the recommended treatment regimens for STS and recurrent
ovarian cancer, was reviewed.
Trabectedin as monotherapy or in combination with
PLD, was not associated with cumulative and/or irreversible toxicities, such as cardiac, pulmonary, renal, or oto-toxicities, often observed with other common chemotherapeutic agents. The most common
adverse drug reactions (ADRs) were myelosuppression and transient hepatic
transaminase increases that were usually not clinically relevant. However,
trabectedin administration should be avoided in patients with severe hepatic impairment. Serious and fatal ADRs were likely to be related to pre-existing conditions.
Doxorubicin or
PLD,
carboplatin,
gemcitabine, or
paclitaxel when administered before
trabectedin, did not seem to influence its pharmacokinetics.
Cytochrome P450 (CYP) 3A4 has an important role in the metabolism of
trabectedin, suggesting a risk of
drug-drug interactions with
trabectedin used in combination with other
CYP3A4 substrates.
Trabectedin has a favorable risk/efficacy profile, even during extended treatment in pretreated patients.