title: The value of trabectedin in the treatment of soft tissue sarcoma.
abstract: Soft tissue sarcomas (STSs) are a group of rare tumors accounting for less than 1% of all adult malignant tumors, a heterogeneous group of more than 50 histological subtypes. Five percent to 30% of STS patients experience local recurrence and 10%-38% present with clinically detectable metastases. Doxorubicin either alone or in combination with ifosfamide has been used as first-line chemotherapy for advanced disease. After failure of first-line chemotherapy, high-dose ifosfamide, gemcitabine + docetaxel, and dacarbazine may be applicable, although high-level evidence is lacking. Trabectedin is a synthetic, marine-derived alkylating agent derived from the Caribbean tunicate, Ecteinascidia turbinata. Several clinical trials have shown that trabectedin has a favorable toxicity profile and is an alternative therapeutic option in adult patients with advanced STS who have not responded to treatment with doxorubicin and ifosfamide. Several clinical trials also recommend the 24-hour intravenous infusion every 3 weeks regimen. The most frequently reported grade 3/4 adverse events were neutropenia and elevated serum levels of AST/ALT. Steroid pretreatment is an effective way of reducing the extent of hepatotoxicity, and steroids are now given routinely before trabectedin administration. Further studies are ongoing to evaluate the efficacy and safety of combination therapy of trabectedin with other agents.
authors.affiliation: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsumine
authors.affiliation: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sudo
keywords: efficacy; safety; soft tissue sarcoma; trabectedin
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2528-33
references.pmid: 21606430
references.citation: J Clin Oncol. 2009 Sep 1;27(25):4188-96
references.pmid: 19652065
references.citation: Lancet Oncol. 2015 Mar;16(3):312-9
references.pmid: 25680558
references.citation: Oncol Lett. 2011 Mar;2(2):315-318
references.pmid: 22866083
references.citation: Invest New Drugs. 2014 Aug;32(4):691-9
references.pmid: 24696229
references.citation: Eur J Cancer. 2006 Jul;42(10 ):1484-90
references.pmid: 16737808
references.citation: Ann Surg. 2012 Feb;255(2):343-7
references.pmid: 22143203
references.citation: Ann Surg Oncol. 2014 Aug;21(8):2484-9
references.pmid: 24756814
references.citation: J Clin Oncol. 1995 Jul;13(7):1600-8
references.pmid: 7541449
references.citation: Lancet. 2012 May 19;379(9829):1879-86
references.pmid: 22595799
references.citation: Mol Cancer Ther. 2009 Feb;8(2):449-57
references.pmid: 19190116
references.citation: Cancer. 1996 Nov 15;78(10):2247-57
references.pmid: 8918421
references.citation: Tumori. 2011 Mar-Apr;97(2):256
references.pmid: 21617728
references.citation: Clin Cancer Res. 2008 Oct 15;14 (20):6656-62
references.pmid: 18927308
references.citation: Clin Cancer Res. 2014 Mar 1;20(5):1190-203
references.pmid: 24277455
references.citation: J Clin Oncol. 2007 Jul 1;25(19):2755-63
references.pmid: 17602081
references.citation: J Clin Oncol. 1999 Jan;17(1):150-7
references.pmid: 10458228
references.citation: Br J Cancer. 2007 Dec 17;97(12 ):1618-24
references.pmid: 18000504
references.citation: Br J Cancer. 2015 Feb 17;112(4):688-92
references.pmid: 25602962
references.citation: Br J Cancer. 2013 Oct 1;109 (7):1717-24
references.pmid: 24022187
references.citation: J Clin Oncol. 1993 Jul;11(7):1276-85
references.pmid: 8315425
references.citation: N Engl J Med. 2005 Aug 18;353(7):701-11
references.pmid: 16107623
references.citation: Invest New Drugs. 2012 Jun;30(3):1193-202
references.pmid: 21484250
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13062-7
references.pmid: 17656556
references.citation: Drugs. 2007;67(15):2257-76
references.pmid: 17927287
references.citation: Pharmacol Ther. 2013 Feb;137(2):216-24
references.pmid: 23085431
references.citation: Eur J Cancer. 2012 Mar;48(4):579-85
references.pmid: 22088484
references.citation: Lancet Oncol. 2007 Jul;8(7):595-602
references.pmid: 17586092
references.citation: Sarcoma. 2002;6(2):69-73
references.pmid: 18521331
references.citation: Br J Cancer. 2014 Aug 12;111(4):646-50
references.pmid: 24755886
references.citation: J Clin Invest. 2012 Mar;122(3):886-98
references.pmid: 22293175
references.citation: Oncogene. 2014 Oct 30;33(44):5201-10
references.pmid: 24213580
references.citation: Lancet Oncol. 2015 Apr;16(4):406-16
references.pmid: 25795406
references.citation: Future Oncol. 2014 Jun;10 (8 Suppl):s1-5
references.pmid: 25048043
references.citation: J Clin Oncol. 2016 Mar 10;34(8):786-93
references.pmid: 26371143
references.citation: Ann Oncol. 2014 Sep;25 Suppl 3:iii102-12
references.pmid: 25210080
references.citation: Eur J Cancer. 2002 Dec;38(18):2397-406
references.pmid: 12460784
references.citation: J Clin Oncol. 2000 Jul;18(14):2676-84
references.pmid: 10894866
references.citation: J Clin Oncol. 2005 Jan 20;23 (3):576-84
references.pmid: 15659504
references.citation: Cochrane Database Syst Rev. 2003;(3):CD003293
references.pmid: 12917960
references.citation: Ann Thorac Surg. 2009 Sep;88(3):877-84; discussion 884-5
references.pmid: 19699915
references.citation: Eur J Cancer. 2015 Apr;51(6):742-50
references.pmid: 25727882
references.citation: Eur J Cancer. 2009 May;45(7):1153-61
references.pmid: 19114300
references.citation: J Clin Oncol. 2004 Mar 1;22(5):890-9
references.pmid: 14990645
references.citation: Cancer Cell. 2013 Feb 11;23 (2):249-62
references.pmid: 23410977
references.citation: Ann Oncol. 2012 Mar;23 (3):771-6
references.pmid: 21642514
references.citation: Cancer. 2003 May 15;97(10):2530-43
references.pmid: 12733153
references.citation: J Am Coll Surg. 2000 Aug;191(2):184-90; discussion 190-1
references.pmid: 10945362
references.citation: Lancet Oncol. 2014 Apr;15(4):415-23
references.pmid: 24618336
references.citation: Eur J Cancer. 2014 Apr;50(6):1137-47
references.pmid: 24512981
references.citation: CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29
references.pmid: 24399786
references.citation: Mol Cancer Ther. 2010 Aug;9(8):2157-63
references.pmid: 20647340
references.citation: J Clin Oncol. 2004 Apr 15;22(8):1480-90
references.pmid: 15084621
references.citation: J Clin Oncol. 1998 Jan;16(1):197-203
references.pmid: 9440743
references.citation: Nat Prod Rep. 2009 Mar;26(3):322-37
references.pmid: 19240944
references.citation: Neoplasia. 2011 Feb;13(2):145-53
references.pmid: 21403840
references.citation: Eur J Cancer. 2012 Nov;48(16):3036-44
references.pmid: 22749255
references.citation: Eur J Cancer. 1997 Feb;33(2):220-5
references.pmid: 9135492
references.citation: Sarcoma. 2015;2015:704124
references.pmid: 26089739
references.citation: Sarcoma. 2013;2013:868973
references.pmid: 24369450
references.citation: Chem Biol. 2011 Aug 26;18(8):988-99
references.pmid: 21867914
references.citation: Eur J Cancer. 2015 Jul;51(10 ):1312-20
references.pmid: 25912752