title: Trabectedin as single agent in relapsed advanced ovarian cancer: results from a retrospective pooled analysis of three phase II trials.
abstract: Three phase II studies evaluated trabectedin monotherapy as second-/third-line therapy in patients with refractory/recurrent ovarian cancer (ROC). Three different schedules were investigated: 3-h infusion every 3 weeks (3-h_q3w), 24-h infusion q3w (24-h_q3w), and 3-h weekly infusion for 3 weeks of a 4-week cycle. This retrospective pooled analysis evaluated the efficacy and the safety profile of trabectedin according to each administered regimen. Data from 295 patients were used to compare weekly versus q3w schedules, and 3-h versus 24-h infusion given q3w. Both q3w regimens showed higher overall response rate (36 vs. 16 %; p = 0.0001), disease control rate (66 vs. 46 %; p = 0.0007), and longer median progression-free survival (5.6 vs. 2.8 months; p < 0.0001) than the weekly schedule. Comparable activity was observed for the 3- and 24-h infusions q3w. Common adverse events were nausea, fatigue, vomiting, transient neutropenia, and transaminase increases. A better safety profile regarding neutropenia, fatigue, and vomiting was seen for the 3-h_q3w regimen as compared to the 24-h_q3w one. Trabectedin given as a single agent q3w as 3-h infusion is the schedule of choice for the treatment of ROC, and its efficacy and safety profile favorably compares with other active salvage treatments.
authors: Gynecological, Head and Neck Cancer Division, Department of Medical Oncology, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. jmcampo@vhebron.net
authors: José María
authors: JM
authors: del Campo
authors: Cristiana
authors: C
authors: Sessa
authors: Carolyn N
authors: CN
authors: Krasner
authors: Jan B
authors: JB
authors: Vermorken
authors: Nicoletta
authors: N
authors: Colombo
authors: Stan
authors: S
authors: Kaye
authors: Martin
authors: M
authors: Gore
authors: Patrik
authors: P
authors: Zintl
authors: Javier
authors: J
authors: Gómez
authors: Trilok
authors: T
authors: Parekh
authors: Youn Choi
authors: YC
authors: Park
authors: Scott
authors: S
authors: McMeekin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
references: Ann Oncol. 2009 Nov;20(11):1794-802
references: 19556318
references: J Clin Oncol. 2010 Jul 1;28(19):3107-14
references: 20516432
references: Invest New Drugs. 2012 Jun;30(3):1193-202
references: 21484250
references: Eur J Cancer. 2001 Jan;37(1):97-105
references: 11165136
references: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references: 15761078
references: Ann Oncol. 2000 Dec;11(12):1531-6
references: 11205459
references: Acta Oncol. 2006;45(4):463-8
references: 16760183
references: Nat Med. 2001 Aug;7(8):961-6
references: 11479630
references: J Clin Oncol. 2003 May 15;21(10 Suppl):129s-132s
references: 12743127
references: J Clin Oncol. 1989 Nov;7(11):1672-6
references: 2509641
references: Invest New Drugs. 2012 Apr;30(2):729-40
references: 20960029
references: Drugs. 2011 Jul 30;71(11):1397-412
references: 21812505
references: Anticancer Drugs. 2007 Jun;18(5):611-7
references: 17414631
references: Gynecol Oncol. 1995 Jan;56(1):75-8
references: 7821851
references: Semin Oncol. 2004 Dec;31(6 Suppl 13):91-105
references: 15717739
references: Gynecol Oncol. 2008 Jun;109(3):346-52
references: 18410954
references: J Chemother. 2004 Nov;16 Suppl 4:98-103
references: 15688622
references: Gynecol Oncol. 1999 Feb;72(2):148-53
references: 10021293
references: Ann Oncol. 1994 Sep;5(7):656-7
references: 7993845
references: J Clin Oncol. 1998 Feb;16(2):405-10
references: 9469322
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: Drugs. 1999;58 Suppl 3:43-9
references: 10711841
references: Ann Oncol. 1998 Dec;9(12):1301-7
references: 9932160
references: Eur J Cancer. 1997 Nov;33(13):2167-70
references: 9470802
references: Int J Clin Oncol. 2008 Aug;13(4):345-8
references: 18704636
references: J Clin Oncol. 1996 Jun;14(6):1957-60
references: 8656266
references: J Clin Oncol. 2010 May 20;28(15):2512-9
references: 20406929
references: J Clin Oncol. 2007 Nov 20;25(33):5165-71
references: 18024863
references: Br J Cancer. 2007 Dec 17;97(12):1618-24
references: 18000504
references: Expert Rev Anticancer Ther. 2010 Jan;10(1):81-8
references: 20014888
references: Ann Oncol. 2005;16 Suppl 8:viii7-viii12
references: 16239238
references: J Clin Oncol. 1991 Mar;9(3):389-93
references: 1999708
references: J Clin Oncol. 1994 Sep;12(9):1748-53
references: 7916038
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: J Clin Oncol. 2005 Mar 20;23(9):1867-74
references: 15774779
references: Cancer Res. 2006 Aug 15;66(16):8155-62
references: 16912194
references: Mol Cancer Ther. 2010 Aug;9(8):2157-63
references: 20647340
references: Gynecol Oncol. 2011 Mar;120(3):454-8
references: 21168198
references: Eur J Cancer. 2008 Mar;44(4):609-18
references: 18243687
references: J Clin Oncol. 2007 Jul 10;25(20):2902-8
references: 17617521
references: J Clin Oncol. 2009 Sep 1;27(25):4188-96
references: 19652065
references: Int J Cancer. 2001 May 15;92(4):583-8
references: 11304695