Trabectedin’s contribution to the treatment of sarcomas

Abstract

Historically, treatment options for soft tissue sarcoma in adults have been limited. Prior to the introduction of trabectedin, only two main cytotoxic drugs were considered active: doxorubicin and ifosfamide (and to a lesser extent dacarbazine). Trabectedin is a unique marine-derived agent with a dual mechanism of action; it shares the mechanisms of action of cytotoxic agents and targeted therapies. The activity of trabectedin in advanced soft tissue sarcoma has been demonstrated in an extensive Phase II clinical trials program in which some interesting new models of use were identified, including maintenance treatment and rechallenge after treatment interruption. After 13 years since trabectedin was first investigated, it continues to be the subject of active research in both academia and industry. Numerous clinical studies currently underway with trabectedin are aiming to resolve a variety of questions in order to optimize its use in clinical practice.

Keywords::

• anthracycline
• cytotoxic
• ifosfamide
• soft tissue sarcoma
• targeted therapy
• trabectedin
• Yondelis^®

Financial & competing interests disclosure

J-Y Blay has received research support and honoraria from PharmaMar S.A., Novartis, Roche, GlaxoSmithKline, MSD, Pfizer and Bayer. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial assistance was provided by Content Ed Net (Madrid, Spain).

Notes

Data taken from [1].

INI1: Integrase interactor 1; KIT: C-Kit or CD117 protein; MPNST: Malignant peripheral nerve sheath tumor; NF1: Neurofibromatosis type 1; PDGFR: PDGF receptor.

A/E RMS: Alveolar/embryonal rhabdomyosarcoma; A,I,C,VAc: Adriamycin, ifosfamide, cyclophosphamide, actinomycin D; CDDP: Cisplatinum; DFSP: Dermatofibrosarcoma protuberans; DTIC: Dacarbazine; ESS: Endometrial stromal sarcoma; EWS: Ewing’s sarcoma; GIST: Gastrointestinal stromal tumor; IGF1R: IGF1 receptor; LMS: Leiomyosarcoma; LPS: Liposarcoma; MTP-PE: Mifamurtide; PVNS: Pigmented villonodular synovitis; topo I inh: Topoisomerase I inhibitor; VEGFR TKI: VEGF receptor tyrosine kinase inhibitor.