Review Article

Trabectedin (Yondelis®) as a Therapeutic Option in Gynecological Cancers: A Focus on its Mechanisms of Action, Clinical Activity and Genomic Predictors of Drug Response

Author(s): Soumaya Souid*, Dorra Aissaoui, Najet Srairi-Abid and Khadija Essafi-Benkhadir

Volume 21, Issue 10, 2020

Page: [996 - 1007] Pages: 12

DOI: 10.2174/1389450121666200128161733

Price: $65


The use of predictive biomarkers provides potential individualized cancer therapeutic options to prevent therapy failure as well as serious toxicities. Several recent studies showed that predictive and prognostic biomarkers are a notable personalized strategy to improve patients’ care in several cancers. Trabectedin (Yondelis®) is a cytotoxic agent, derived from a marine organism, harbouring a significant antitumor activity against several cancers such as soft tissue sarcoma, ovarian, and breast cancers. Recently and with the advent of molecular genetic testing, BRCA mutational status was found as an important predictor of response to this anticancer drug, especially in gynecological cancers. The aim of this updated review is to discuss the mechanisms of action of trabectedin against the wellknown cancer hallmarks described until today. The current advances were also examined related to genomic biomarkers that can be used in the future to predict the efficacy of this potent anticancer natural molecule in various gynecological cancers.

Keywords: Trabectedin, gynecological cancers, ovarian cancer, uterine leiomyosarcoma, predictive biomarkers.

Graphical Abstract
Chudasama P, Mughal SS, Sanders MA, et al. Integrative genomic and transcriptomic analysis of leiomyosarcoma. Nat Commun 2018; 9(1): 144.
[] [PMID: 29321523]
del Carmen MG, Rice LW. Underrepresentation of women in clinical trials: why gynecologic oncologists are worried. Obstet Gynecol 2015; 125(3): 616-9.
[] [PMID: 25730224]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[] [PMID: 30207593]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66(1): 7-30.
[] [PMID: 26742998]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
[] [PMID: 30620402]
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-86.
[] [PMID: 25220842]
Baldwin LA, Huang B, Miller RW, et al. Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol 2012; 120(3): 612-8.
[] [PMID: 22914471]
Fortner RT, Poole EM, Wentzensen NA, et al. Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium. Int J Cancer 2019; 145(1): 58-69.
[] [PMID: 30561796]
Ricci S, Stone RL, Fader AN. Uterine leiomyosarcoma: Epidemiology, contemporary treatment strategies and the impact of uterine morcellation. Gynecol Oncol 2017; 145(1): 208-16.
[] [PMID: 28209496]
Seagle BL, Sobecki-Rausch J, Strohl AE, Shilpi A, Grace A, Shahabi S. Prognosis and treatment of uterine leiomyosarcoma: A National Cancer Database study. Gynecol Oncol 2017; 145(1): 61-70.
[] [PMID: 28317559]
Giuntoli RL II, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol 2003; 89(3): 460-9.
[] [PMID: 12798712]
Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 1993; 71(4)(Suppl.): 1702-9.
[] [PMID: 8381710]
Foley OW, Rauh-Hain JA, Clemmer J, et al. Trends in the treatment of uterine leiomyosarcoma in the Medicare population. Int J Gynecol Cancer 2015; 25(3): 453-8.
[] [PMID: 25628107]
Kurman RJ, Zaino RJ, Norris HJ. Endometrial carcinoma Blaustein’s pathology of the female genital tract. Springer 1994; pp. 439-86.
Amaral R, dos Santos S, Andrade L, Severino P, Carvalho A. Natural Products as Treatment against Cancer: A Historical and Current Vision. Clin Oncol (R Coll Radiol) 2019; 4: 1562.
Wieser V, Marth C. Resistance to chemotherapy and anti-angiogenic therapy in ovarian cancer. memo -. Mag Eur Med Oncol 2019; 12(2): 144-8.
Dunton CJ. Management of treatment-related toxicity in advanced ovarian cancer. Oncologist 2002; 7(Suppl. 5): 11-9.
[] [PMID: 12324629]
Aissaoui D, Mlayah-Bellalouna S, Jebali J, et al. Functional role of Kv1.1 and Kv1.3 channels in the neoplastic progression steps of three cancer cell lines, elucidated by scorpion peptides. Int J Biol Macromol 2018; 111: 1146-55.
[] [PMID: 29415410]
Mohyeldin MM, Akl MR, Siddique AB, Hassan HM, El Sayed KA. The marine-derived pachycladin diterpenoids as novel inhibitors of wild-type and mutant EGFR. Biochem Pharmacol 2017; 126: 51-68.
[] [PMID: 27940262]
Siddique AB, Ebrahim HY, Akl MR, et al. (-)-Oleocanthal combined with lapatinib treatment synergized against her-2 positive breast cancer in vitro and in vivo. Nutrients 2019; 11(2) E412
[] [PMID: 30781364]
Souid S, Elsayed HE, Ebrahim HY, et al. 131 -Oxophorbine protopheophorbide A from Ziziphus lotus as a novel mesenchymal-epithelial transition factor receptor inhibitory lead for the control of breast tumor growth in vitro and in vivo. Mol Carcinog 2018; 57(11): 1507-24.
[] [PMID: 29978911]
Calcabrini C, Catanzaro E, Bishayee A, Turrini E, Fimognari C. Marine sponge natural products with anticancer potential: An updated review. Mar Drugs 2017; 15(10): 310.
[] [PMID: 29027954]
Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 2015; 14(2): 111-29.
[] [PMID: 25614221]
Khalid EB, Ayman EE, Rahman H, Abdelkarim G, Najda A. Natural products against cancer angiogenesis. Tumour Biol 2016; 37(11): 14513-36.
[] [PMID: 27651162]
Lin Z, Zhang Q, Luo W. Angiogenesis inhibitors as therapeutic agents in cancer: Challenges and future directions. Eur J Pharmacol 2016; 793: 76-81.
[] [PMID: 27840192]
Rodrigues T, Reker D, Schneider P, Schneider G. Counting on natural products for drug design. Nat Chem 2016; 8(6): 531-41.
[] [PMID: 27219696]
Teplinsky E, Herzog TJ. The efficacy of trabectedin in treating ovarian cancer. Expert Opin Pharmacother 2017; 18(3): 313-23.
[] [PMID: 28140689]
Mousa SA, Sudha T, Davis PJ. Anti-angiogenesis therapy and its combination with chemotherapy: impact on primary tumor and its metastasis anti-angiogenesis strategies in cancer therapeutics. Elsevier 2017; pp. 147-63.
Tumini E, Herrera-Moyano E, San Martín-Alonso M, Barroso S, Galmarini CM, Aguilera A. The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability. Mol Cancer Res 2019; 17(3): 773-82.
[] [PMID: 30552231]
Kalimutho M, Nones K, Srihari S, Duijf PHG, Waddell N, Khanna KK. Patterns of genomic instability in breast cancer. Trends Pharmacol Sci 2019; 40(3): 198-211.
[] [PMID: 30736983]
Krzyzanowski PM, Sircoulomb F, Yousif F, et al. Regional perturbation of gene transcription is associated with intrachromosomal rearrangements and gene fusion transcripts in high grade ovarian cancer. Sci Rep 2019; 9(1): 3590.
[] [PMID: 30837567]
D’Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther 2010; 9(8): 2157-63.
[] [PMID: 20647340]
Ray-Coquard I. Biology of ovarian cancer and trabectedin mechanism of action. Future Oncol 2013; 9(12)(Suppl.): 11-7.
[] [PMID: 24195525]
Lee DY, Staddon AP, Shabason JE, Sebro R. Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development. Cancer Med 2019; 8(2): 585-92.
[] [PMID: 30632291]
Pereira F. Have marine natural product drug discovery efforts been productive and how can we improve their efficiency?. Taylor & Francis 2019.
El Bairi K, Amrani M, Afqir S. Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers. Cancer Med 2018; 7(6): 2221-46.
[] [PMID: 29732738]
Cucè M, Gallo Cantafio ME, Siciliano MA, et al. Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma. J Hematol Oncol 2019; 12(1): 32.
[] [PMID: 30898137]
D’Incalci M, Badri N, Galmarini CM, Allavena P. Trabectedin, a drug acting on both cancer cells and the tumour microenvironment. Br J Cancer 2014; 111(4): 646-50.
[] [PMID: 24755886]
Belgiovine C, Bello E, Liguori M, et al. Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models. Br J Cancer 2017; 117(5): 628-38.
[] [PMID: 28683469]
Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 2013; 23(2): 249-62.
[] [PMID: 23410977]
Germano G, Frapolli R, Simone M, et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res 2010; 70(6): 2235-44.
[] [PMID: 20215499]
El Bairi K, Atanasov AG, Amrani M, Afqir S. The arrival of predictive biomarkers for monitoring therapy response to natural compounds in cancer drug discovery. Biomed Pharmacother 2019; 109: 2492-8.
[] [PMID: 30551510]
Larsen AK, Galmarini CM, D’Incalci M. Unique features of trabectedin mechanism of action. Cancer Chemother Pharmacol 2016; 77(4): 663-71.
[] [PMID: 26666647]
Bonfanti M, La Valle E, Fernandez Sousa Faro JM, et al. Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anticancer Drug Des 1999; 14(3): 179-86.
[PMID: 10500494]
Jin S, Gorfajn B, Faircloth G, Scotto KW. Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation. Proc Natl Acad Sci USA 2000; 97(12): 6775-9.
[] [PMID: 10841572]
Minuzzo M, Marchini S, Broggini M, Faircloth G, D’Incalci M, Mantovani R. Interference of transcriptional activation by the antineoplastic drug ecteinascidin-743. Proc Natl Acad Sci USA 2000; 97(12): 6780-4.
[] [PMID: 10841573]
Damia G, Imperatori L, Stefanini M, D’Incalci M. Sensitivity of CHO mutant cell lines with specific defects in nucleotide excision repair to different anti-cancer agents. Int J Cancer 1996; 66(6): 779-83.
[<779:AID-IJC12>3.0.CO;2-Z] [PMID: 8647649]
Takebayashi Y, Pourquier P, Zimonjic DB, et al. Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med 2001; 7(8): 961-6.
[] [PMID: 11479630]
Zewail-Foote M, Li V-S, Kohn H, Bearss D, Guzman M, Hurley LH. The inefficiency of incisions of ecteinascidin 743-DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent. Chem Biol 2001; 8(11): 1033-49.
[] [PMID: 11731295]
Tavecchio M, Simone M, Erba E, et al. Role of homologous recombination in trabectedin-induced DNA damage. Eur J Cancer 2008; 44(4): 609-18.
[] [PMID: 18243687]
Herrero AB, Martín-Castellanos C, Marco E, Gago F, Moreno S. Cross-talk between nucleotide excision and homologous recombination DNA repair pathways in the mechanism of action of antitumor trabectedin. Cancer Res 2006; 66(16): 8155-62.
[] [PMID: 16912194]
Poveda A, Vergote I, Tjulandin S, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol 2011; 22(1): 39-48.
[] [PMID: 20643862]
Schoffski P, Casali P, Taron M, Van Oosterom A, Judson I, Grosso F, et al. DNA repair functionality modulates the clinical outcomeof patients with advanced sarcoma treated with trabectedin (ET- 743). Journal of Clinical Oncology 2006; 24(18_suppl): 9522.
Erba E, Bergamaschi D, Bassano L, et al. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer 2001; 37(1): 97-105.
[] [PMID: 11165136]
Ventriglia J, Paciolla I, Cecere SC, et al. Trabectedin in Ovarian Cancer: is it now a Standard of Care? Clin Oncol (R Coll Radiol) 2018; 30(8): 498-503.
[] [PMID: 29429842]
Monk BJ, Ghatage P, Parekh T, et al. Effect of BRCA1 and XPG mutations on treatment response to trabectedin and pegylated liposomal doxorubicin in patients with advanced ovarian cancer: exploratory analysis of the phase 3 OVA-301 study. Ann Oncol 2015; 26(5): 914-20.
[] [PMID: 25722380]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. cell 2011; 144(5): 646-74.
Kulbe H, Chakravarty P, Leinster DA, et al. Australian Ovarian Cancer Study Group. A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Res 2012; 72(1): 66-75.
[] [PMID: 22065722]
Rubio C, Munera-Maravilla E, Lodewijk I, et al. Macrophage polarization as a novel weapon in conditioning tumor microenvironment for bladder cancer: can we turn demons into gods? Clin Transl Oncol 2019; 21(4): 391-403.
[] [PMID: 30291519]
Allavena P, Mantovani A. Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment. Clin Exp Immunol 2012; 167(2): 195-205.
[] [PMID: 22235995]
Motz GT, Coukos G. The parallel lives of angiogenesis and immunosuppression: cancer and other tales. Nat Rev Immunol 2011; 11(10): 702-11.
[] [PMID: 21941296]
Cheng H, Wang Z, Fu L, Xu T. Macrophage Polarization in the Development and Progression of Ovarian Cancers: An Overview. Front Oncol 2019; 9: 421.
[] [PMID: 31192126]
Berek JS, Chung C, Kaldi K, Watson JM, Knox RM, Martínez-Maza O. Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol 1991; 164(4): 1038-42.
[] [PMID: 2014824]
Scambia G, Testa U, Benedetti Panici P, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995; 71(2): 354-6.
[] [PMID: 7841052]
Watson JM, Sensintaffar JL, Berek JS, Martínez-Maza O. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990; 50(21): 6959-65.
[PMID: 2208162]
Dossi R, Frapolli R, Di Giandomenico S, et al. Antiangiogenic activity of trabectedin in myxoid liposarcoma: involvement of host TIMP-1 and TIMP-2 and tumor thrombospondin-1. Int J Cancer 2015; 136(3): 721-9.
[PMID: 24917554]
Leporini C, Patanè M, Saullo F, et al. A comprehensive safety evaluation of trabectedin and drug-drug interactions of trabectedin-based combinations. BioDrugs 2014; 28(6): 499-511.
[] [PMID: 25209722]
Allavena P, Signorelli M, Chieppa M, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res 2005; 65(7): 2964-71.
[] [PMID: 15805300]
Carminati L, Pinessi D, Borsotti P, et al. Antimetastatic and antiangiogenic activity of trabectedin in cutaneous melanoma. Carcinogenesis 2019; 40(2): 303-12.
[] [PMID: 30544170]
Guerriero JL. Macrophages: the road less traveled, changing anticancer therapy. Trends Mol Med 2018; 24(5): 472-89.
[] [PMID: 29655673]
Sawa-Wejksza K, Kandefer-Szerszeń M. Tumor-Associated Macrophages as Target for Antitumor Therapy. Arch Immunol Ther Exp (Warsz) 2018; 66(2): 97-111.
[] [PMID: 28660349]
Mora J, Mertens C, Meier JK, Fuhrmann DC, Brüne B, Jung M. Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity. Cells 2019; 8(5): 445.
[] [PMID: 31083487]
Larionova I, Cherdyntseva N, Liu T, Patysheva M, Rakina M, Kzhyshkowska J. Interaction of tumor-associated macrophages and cancer chemotherapy. OncoImmunology 2019; 8(7) 1596004
[] [PMID: 31143517]
D’Incalci M, Zambelli A. Trabectedin for the treatment of breast cancer. Expert Opin Investig Drugs 2016; 25(1): 105-15.
[] [PMID: 26592307]
Liguori M, Buracchi C, Pasqualini F, et al. Functional TRAIL receptors in monocytes and tumor-associated macrophages: A possible targeting pathway in the tumor microenvironment. Oncotarget 2016; 7(27): 41662-76.
[] [PMID: 27191500]
Ovais M, Guo M, Chen C. Tailoring Nanomaterials for Targeting Tumor-Associated Macrophages. Adv Mater 2019; 31(19) e1808303
[] [PMID: 30883982]
Peraza DA, Garcia-Redondo AB, Povo-Retana A, Arias S, Briones AM, Boscá L, et al. Re-education of tumor associated macrophages by trabectedin. Biophys J 2019; 116(3): 539a-40a.
Mascilini F, Amadio G, Di Stefano MG, et al. Clinical utility of trabectedin for the treatment of ovarian cancer: current evidence. OncoTargets Ther 2014; 7: 1273-84.
[PMID: 25050069]
Colmegna B, Uboldi S, Frapolli R, et al. Increased sensitivity to platinum drugs of cancer cells with acquired resistance to trabectedin. Br J Cancer 2015; 113(12): 1687-93.
[] [PMID: 26633559]
Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 2017; 14(7): 399-416.
[] [PMID: 28117416]
D’Angelo D, Borbone E, Palmieri D, et al. The impairment of the High Mobility Group A (HMGA) protein function contributes to the anticancer activity of trabectedin. Eur J Cancer 2013; 49(5): 1142-51.
[] [PMID: 23149213]
Hollebecque A, Adenis A, Taieb S, Lebedinsky C, Penel N. Inadequacy of size-based response criteria to assess the efficacy of trabectedin among metastatic sarcoma patients. Invest New Drugs 2010; 28(4): 529-30.
[] [PMID: 19430728]
Sanfilippo R, Casali PG. The intriguing patterns of tumor response to trabectedin. Expert review of anticancer therapy 2013; 13(sup1): 21-4.
Lee JM, Ledermann JA, Kohn EC. PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol 2014; 25(1): 32-40.
[] [PMID: 24225019]
Monk BJ, Lorusso D, Italiano A, et al. Trabectedin as a chemotherapy option for patients with BRCA deficiency. Cancer Treat Rev 2016; 50: 175-82.
[] [PMID: 27710871]
Orban TI, Olah E. Emerging roles of BRCA1 alternative splicing. Molecular pathology: MP 2003; 56(4): 191-7.
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474(7353): 609-15.
[] [PMID: 21720365]
Lorusso D, Scambia G, Pignata S, et al. Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial. Ann Oncol 2016; 27(3): 487-93.
[] [PMID: 26681678]
McAlpine JN, Porter H, Kobel M, Nelson BH, Prentice LM, Kalloger SE, et al. BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma. Modern pathology: an official journal of the United States and Canadian Academy of Pathology. Inc 2012; 25(5): 740-50.
Venkitaraman AR. Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment. Annu Rev Pathol 2009; 4: 461-87.
[] [PMID: 18954285]
Arun B, Vogel KJ, Lopez A, et al. High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers. Cancer Prev Res (Phila) 2009; 2(2): 122-7.
[] [PMID: 19174581]
Delaloge S, Wolp-Diniz R, Byrski T, et al. Activity of trabectedin in germline BRCA1/2-mutated metastatic breast cancer: results of an international first-in-class phase II study. Ann Oncol 2014; 25(6): 1152-8.
[] [PMID: 24692579]
Ghouadni A, Delaloge S, Lardelli P, et al. Higher antitumor activity of trabectedin in germline BRCA2 carriers with advanced breast cancer as compared to BRCA1 carriers: A subset analysis of a dedicated phase II trial. Breast 2017; 34: 18-23.
[] [PMID: 28467918]
Awada A, Cortés J, Martín M, et al. Phase 2 study of trabectedin in patients with hormone receptor-positive, her-2-negative, advanced breast carcinoma according to expression of xeroderma pigmentosum g gene. Clin Breast Cancer 2016; 16(5): 364-71.
[] [PMID: 27266804]
Blum JL, Gonçalves A, Efrat N, et al. A phase II trial of trabectedin in triple-negative and HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat 2016; 155(2): 295-302.
[] [PMID: 26749361]
Italiano A, Laurand A, Laroche A, et al. ERCC5/XPG, ERCC1, and BRCA1 gene status and clinical benefit of trabectedin in patients with soft tissue sarcoma. Cancer 2011; 117(15): 3445-56.
[] [PMID: 21287534]
Laroche-Clary A, Chaire V, Le Morvan V, et al. BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma patients. Br J Cancer 2015; 112(4): 688-92.
[] [PMID: 25602962]
Massuti B, Cobo M, Camps C, et al. Trabectedin in patients with advanced non-small-cell lung cancer (NSCLC) with XPG and/or ERCC1 overexpression and BRCA1 underexpression and pretreated with platinum. Lung Cancer 2012; 76(3): 354-61.
[] [PMID: 22197612]
Sessa C, De Braud F, Perotti A, et al. Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails. J Clin Oncol 2005; 23(9): 1867-74.
Schoffski P, Taron M, Jimeno J, Grosso F, Sanfilipio R, Casali PG, et al. Predictive impact of DNA repair functionality on clinical outcome of advanced sarcoma patients treated with trabectedin: a retrospective multicentric study. 2011; 47(7): 1006-2.
del Campo JM, Sessa C, Krasner CN, et al. Trabectedin as single agent in relapsed advanced ovarian cancer: results from a retrospective pooled analysis of three phase II trials. Med Oncol 2013; 30(1): 435.
[] [PMID: 23397080]
O’Cearbhaill R, Zhou Q, Iasonos A, et al. The prophylactic conversion to an extended infusion schedule and use of premedication to prevent hypersensitivity reactions in ovarian cancer patients during carboplatin retreatment. Gynecol Oncol 2010; 116(3): 326-31.
[] [PMID: 19944454]
Casado A, Callata HR, Manzano A, et al. Trabectedin for reversing platinum resistance and resensitization to platinum in patients with recurrent ovarian cancer. Future Oncol 2019; 15(3): 271-80.
[] [PMID: 30465613]
Lorusso D, Cirillo F, Mancini M, et al. The different impact of BRCA mutations on the survival of epithelial ovarian cancer patients: a retrospective single-center experience. Oncology 2013; 85(2): 122-7.
[] [PMID: 23941904]
Sanctis R De, Marrari A, Marchetti S, et al. Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma. Drug design, development and therapy 2015; 9: 5785-91.
Del Campo JM, Roszak A, Bidzinski M, et al. Yondelis Ovarian Cancer Group. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol 2009; 20(11): 1794-802.
[] [PMID: 19556318]
Krasner CN, McMeekin DS, Chan S, et al. A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer 2007; 97(12): 1618-24.
[] [PMID: 18000504]
Colombo N. When nonplatinum is the answer: the role of trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. Future Oncol 2017; 13(23s): 23-9.
[] [PMID: 29020821]
Rubio Pérez MJ. Effect of the Combination of Trabectedin and Pegylated Liposomal Doxorubicin in a BRCA2 Mutation Carrier with Recurrent Platinum-Sensitive Ovarian Cancer. Case Rep Oncol 2017; 10(2): 433-7.
[] [PMID: 28626402]
Bongiovanni A, Riva N, Ricci M, et al. Long-lasting activity of trabectedin in refractory uterine leiomyosarcoma: a case report. BMC Cancer 2015; 15: 998.
[] [PMID: 26695071]
De Sanctis R, Marrari A, Marchetti S, et al. Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma. Drug Des Devel Ther 2015; 9: 5785-91.
[] [PMID: 26604682]
Demetri GD, von Mehren M, Jones RL, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase iii randomized multicenter clinical trial. J Clin Oncol 2016; 34(8): 786-93.
[] [PMID: 26371143]
Monk BJ, Blessing JA, Street DG, Muller CY, Burke JJ, Hensley ML. A phase II evaluation of trabectedin in the treatment of advanced, persistent, or recurrent uterine leiomyosarcoma: a gynecologic oncology group study. Gynecol Oncol 2012; 124(1): 48-52.
[] [PMID: 21996263]
Amant F, Lorusso D, Mustea A, Duffaud F, Pautier P. Management Strategies in Advanced Uterine Leiomyosarcoma: Focus on Trabectedin. Sarcoma 2015; 2015, 704124
[] [PMID: 26089739]
Payne MJ, Macpherson RE, Bradley KM, Hassan AB. Trabectedin in Advanced High-Grade Uterine Leiomyosarcoma: A Case Report Illustrating the Value of (18)FDG-PET-CT in Assessing Treatment Response. Case Rep Oncol 2014; 7(1): 132-8.
[] [PMID: 24707261]
Pautier P, Floquet A, Chevreau C, et al. French Sarcoma Group. Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial. Lancet Oncol 2015; 16(4): 457-64.
[] [PMID: 25795402]
Bui-Nguyen B, Butrynski JE, Penel N, Blay JY, Isambert N, Milhem M, et al. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: the TRUSTS trial. European journal of cancer (Oxford, England: 1990) 2015; 51(10): 1312-20.
Garcia-Carbonero R, Supko JG, Maki RG, et al. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 2005; 23(24): 5484-92.
[] [PMID: 16110008]
Garcia-Carbonero R, Supko JG, Manola J, et al. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol 2004; 22(8): 1480-90.
[] [PMID: 15084621]
Le Cesne A, Blay JY, Judson I, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol 2005; 23(3): 576-84.
[] [PMID: 15659504]
Yovine A, Riofrio M, Blay JY, et al. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol 2004; 22(5): 890-9.
[] [PMID: 14990645]
Hensley ML, Patel SR, von Mehren M, et al. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol 2017; 146(3): 531-7.
[] [PMID: 28651804]
Movva S, Wen W, Chen W, et al. Multi-platform profiling of over 2000 sarcomas: identification of biomarkers and novel therapeutic targets. Oncotarget 2015; 6(14): 12234-47.
[] [PMID: 25906748]
Pompili L, Leonetti C, Biroccio A, Salvati E. Diagnosis and treatment of ALT tumors: is Trabectedin a new therapeutic option? Journal of experimental & clinical cancer research. CR (East Lansing Mich) 2017; 36(1): 189.
Henson JD, Lau LM, Koch S, Martin La Rotta N, Dagg RA, Reddel RR. The C-Circle Assay for alternative-lengthening-of-telomeres activity. Methods 2017; 114: 74-84.
[] [PMID: 27595911]
Leung JW, Ghosal G, Wang W, et al. Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress. J Biol Chem 2013; 288(9): 6342-50.
[] [PMID: 23329831]
Pickett HA, Reddel RR. The role of telomere trimming in normal telomere length dynamics. Cell Cycle 2012; 11(7): 1309-15.
[] [PMID: 22421147]
Liau JY, Tsai JH, Jeng YM, Lee JC, Hsu HH, Yang CY. Leiomyosarcoma with alternative lengthening of telomeres is associated with aggressive histologic features, loss of ATRX expression, and poor clinical outcome. Am J Surg Pathol 2015; 39(2): 236-44.
[] [PMID: 25229770]
Gocha AR, Nuovo G, Iwenofu OH, Groden J. Human sarcomas are mosaic for telomerase-dependent and telomerase-independent telomere maintenance mechanisms: implications for telomere-based therapies. Am J Pathol 2013; 182(1): 41-8.
[] [PMID: 23260199]
Lee YK, Park NH, Lee H. Prognostic value of alternative lengthening of telomeres-associated biomarkers in uterine sarcoma and uterine carcinosarcoma. International journal of gynecological cancer: official journal of the International Gynecological Cancer Society 2012; 22(3): 434-1.
Pignochino Y, Capozzi F, D’Ambrosio L, et al. PARP1 expression drives the synergistic antitumor activity of trabectedin and PARP1 inhibitors in sarcoma preclinical models. Mol Cancer 2017; 16(1): 86.
[] [PMID: 28454547]
Schroeder BA, Rodler ET, Loggers ET, Pollack SM, Jones RL. Clinical benefit of trabectedin in uterine adenosarcoma. Med Oncol 2013; 30(2): 501.
[] [PMID: 23456619]
Nathenson MJ, Conley AP, Lin H, Fleming N, Ravi V. Treatment of Recurrent or Metastatic Uterine Adenosarcoma. Sarcoma 2017; 2017, 4680273
[] [PMID: 29445312]
Arend RC, Toboni MD, Montgomery AM, et al. Systemic treatment of metastatic/recurrent uterine leiomyosarcoma: a changing paradigm. Oncologist 2018; 23(12): 1533-45.
[] [PMID: 30139839]
Tantari M, Barra F, Di Domenico S, et al. Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas. Expert Opin Pharmacother 2019; 20(6): 713-23.
[] [PMID: 30724615]
Odunsi K. Immunotherapy in ovarian cancer. Ann Oncol 2017; 28(suppl_8): viii1-7.
Ventriglia J, Paciolla I, Pisano C, et al. Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives. Cancer Treat Rev 2017; 59: 109-16.
[] [PMID: 28800469]
Suh DH, Kim M, Lee KH, et al. Major clinical research advances in gynecologic cancer in 2017. J Gynecol Oncol 2018; 29(2) e31
[] [PMID: 29468855]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy