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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Trabectedin in Cancers: Mechanisms and Clinical Applications

Author(s): Jiali Wang, Pengfei Wang, Zheng Zeng, Caiji Lin, Yiru Lin, Danli Cao, Wenqing Ma, Wenwen Xu, Qian Xiang, Lingjie Luo, Wenxue Wang, Yongwei Shi, Zixiang Gao, Yufan Zhao, Huidi Liu* and Shu-Lin Liu*

Volume 28, Issue 24, 2022

Published on: 13 July, 2022

Page: [1949 - 1965] Pages: 17

DOI: 10.2174/1381612828666220526125806

Price: $65


Trabectedin, a tetrahydroisoquinoline alkaloid, is the first marine antineoplastic agent approved with special anticancer mechanisms involving DNA binding, DNA repair pathways, transcription regulation and regulation of the tumor microenvironment. It has favorable clinical applications, especially for the treatment of patients with advanced soft tissue sarcoma, who failed in anthracyclines and ifosfamide therapy or could not receive these agents. Currently, trabectedin monotherapy regimen and regimens of combined therapy with other agents are both widely used for the treatment of malignancies, including soft tissue sarcomas, ovarian cancer, breast cancer, and non-small-cell lung cancer. In this review, we have summarized the basic information and some updated knowledge on trabectedin, including its molecular structure, metabolism in various cancers, pharmaceutical mechanisms, clinical applications, drug combination, and adverse reactions, along with prospects of its possibly more optimal use in cancer treatment.

Keywords: Trabectedin, anticancer, tissue sarcomas, combined drug use, malignancies, antineoplastic agent, tumor microenvironment.

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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]
Wang Y, Han Q, Zhang H. Evaluation of the toxicity of 5-fluorouracil on three digestive enzymes from the view of side effects. Spectrochim Acta A Mol Biomol Spectrosc 2019; 220117105
[] [PMID: 31141767]
Shahid F, Farooqui Z, Khan F. Cisplatin-induced gastrointestinal toxicity: An update on possible mechanisms and on available gastroprotective strategies. Eur J Pharmacol 2018; 827: 49-57.
[] [PMID: 29530589]
Frączek N, Bronisz I, Pietryka M, et al. An outline of main factors of drug resistance influencing cancer therapy. J Chemother 2016; 28(6): 457-64.
[] [PMID: 27545330]
Lichota A, Gwozdzinski K. Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 2018; 19(11): 19.
[] [PMID: 30423952]
Shim JS, Lee HS, Shin J, Kwon HJ, Psammaplin A. A marine natural product, inhibits aminopeptidase N and suppresses angiogenesis in vitro. Cancer Lett 2004; 203(2): 163-9.
[] [PMID: 14732224]
Matulja D, Wittine K, Malatesti N, et al. Marine natural products with high anticancer activities. Curr Med Chem 2020; 27(8): 1243-307.
[] [PMID: 31931690]
Kindler HL, Tothy PK, Wolff R, et al. Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers. Invest New Drugs 2005; 23(5): 489-93.
[] [PMID: 16133801]
Gordon EM, Sankhala KK, Chawla N, Chawla SP. Trabectedin for soft tissue sarcoma: Current status and future perspectives. Adv Ther 2016; 33(7): 1055-71.
[] [PMID: 27234989]
Del Campo JM, Muñoz-Couselo E, Diaz de Corcuera I, Oaknin A. Trabectedin combined with liposomal doxorubicin in women with relapsed ovarian cancer. Expert Rev Anticancer Ther 2010; 10(6): 795-805.
[] [PMID: 20553205]
Martinez EJ, Corey EJ. A new, more efficient, and effective process for the synthesis of a key pentacyclic intermediate for production of ecteinascidin and phthalascidin antitumor agents. Org Lett 2000; 2(7): 993-6.
[] [PMID: 10768205]
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]
D’Incalci M. Trabectedin mechanism of action: What’s new? Future Oncol 2013; 9(12)(Suppl.): 5-10.
[] [PMID: 24195524]
Demetri GD, Chawla SP, von Mehren M, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: Results of a randomized phase II study of two different schedules. J Clin Oncol 2009; 27(25): 4188-96.
[] [PMID: 19652065]
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]
Barone A, Chi DC, Theoret MR, et al. FDA approval summary: Trabectedin for unresectable or metastatic liposarcoma or leiomyosarcoma following an anthracycline-containing regimen. Clin Cancer Res 2017; 23(24): 7448-53.
[] [PMID: 28774898]
Kobayashi H, Iwata S, Wakamatsu T, et al. Efficacy and safety of trabectedin for patients with unresectable and relapsed soft-tissue sarcoma in Japan: A japanese musculoskeletal oncology group study. Cancer 2020; 126(6): 1253-63.
[] [PMID: 31825533]
Carter NJ, Keam SJ. Trabectedin: A review of its use in the management of soft tissue sarcoma and ovarian cancer. Drugs 2007; 67(15): 2257-76.
[] [PMID: 17927287]
D’Incalci M, Zambelli A. Trabectedin for the treatment of breast cancer. Expert Opin Investig Drugs 2016; 25(1): 105-15.
[] [PMID: 26592307]
Hendriks HR, Fiebig HH, Giavazzi R, Langdon SP, Jimeno JM, Faircloth GT. High antitumour activity of ET743 against human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer. Ann Oncol 1999; 10(10): 1233-40.
[] [PMID: 10586342]
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]
Romano M, Della Porta MG, Gallì A, et al. Antitumour activity of trabectedin in myelodysplastic/myeloproliferative neoplasms. Br J Cancer 2017; 116(3): 335-43.
[] [PMID: 28072764]
Kawano M, Mabuchi S, Kishimoto T, et al. Combination treatment with trabectedin and irinotecan or topotecan has synergistic effects against ovarian clear cell carcinoma cells. Int J Gynecol Cancer 2014; 24(5): 829-37.
[] [PMID: 24844217]
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]
Marchetti C, Musella A, Romito A, et al. Short-Infusion trabectedin in heavily pretreated ovarian cancer patients: A single-institution experience. Oncology 2017; 93(6): 359-66.
[] [PMID: 28946142]
Colombo N. Recurrent ovarian cancer 8 months after induction and bevacizumab consolidation: Rationale for using trabectedin + pegylated liposomal doxorubicin in second line. Expert Rev Anticancer Ther 2018; 18(sup1): 13-7.
[] [PMID: 30223694]
Jimenez PC, Wilke DV, Branco PC, et al. Enriching cancer pharmacology with drugs of marine origin. Br J Pharmacol 2020; 177(1): 3-27.
[] [PMID: 31621891]
Jones RL, Maki RG, Patel SR, et al. Safety and efficacy of trabectedin when administered in the inpatient versus outpatient setting: Clinical considerations for outpatient administration of trabectedin. Cancer 2019; 125(24): 4435-41.
[] [PMID: 31503332]
Cuevas C, Francesch A. Development of yondelis (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat Prod Rep 2009; 26(3): 322-37.
[] [PMID: 19240944]
Soares DG, Machado MS, Rocca CJ, et al. Trabectedin and its C subunit modified analogue PM01183 attenuate nucleotide excision repair and show activity toward platinum-resistant cells. Mol Cancer Ther 2011; 10(8): 1481-9.
[] [PMID: 21622731]
Perez-Ruixo JJ, Zannikos P, Hirankarn S, et al. Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis) in cancer patients. Clin Pharmacokinet 2007; 46(10): 867-84.
[] [PMID: 17854236]
Brandon EF, Sparidans RW, Guijt KJ, et al. In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest New Drugs 2006; 24(1): 3-14.
[] [PMID: 16379042]
Huang SM, Strong JM, Zhang L, et al. New era in drug interaction evaluation: US food and drug administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol 2008; 48(6): 662-70.
[] [PMID: 18378963]
Vermeir M, Hemeryck A, Cuyckens F, et al. In vitro studies on the metabolism of trabectedin (YONDELIS) in monkey and man, including human CYP reaction phenotyping. Biochem Pharmacol 2009; 77(10): 1642-54.
[] [PMID: 19426702]
Ray-Coquard I. Trabectedin mechanism of action and platinum resistance: Molecular rationale. Future Oncol 2017; 13(23s): 17-21.
[] [PMID: 29020822]
D’Incalci M, Erba E, Damia G, et al. Unique features of the mode of action of ET-743. Oncologist 2002; 7(3): 210-6.
[] [PMID: 12065793]
Zewail-Foote M, Hurley LH. Ecteinascidin 743: A minor groove alkylator that bends DNA toward the major groove. J Med Chem 1999; 42(14): 2493-7.
[] [PMID: 10411470]
Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the caribbean tunicate ecteinascidia turbinata. Biochemistry 1996; 35(41): 13303-9.
[] [PMID: 8873596]
Hurley LH, Zewail-Foote M. The antitumor agent ecteinascidin 743: characterization of its covalent DNA adducts and chemical stability. Adv Exp Med Biol 2001; 500: 289-99.
[] [PMID: 11764956]
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]
Soares DG, Escargueil AE, Poindessous V, et al. Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743. Proc Natl Acad Sci USA 2007; 104(32): 13062-7.
[] [PMID: 17656556]
Sakai R, Rinehart KL, Guan Y, Wang AH. Additional antitumor ecteinascidins from a Caribbean tunicate: Crystal structures and activities in vivo. Proc Natl Acad Sci USA 1992; 89(23): 11456-60.
[] [PMID: 1454834]
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]
Di Giandomenico S, Frapolli R, Bello E, et al. Mode of action of trabectedin in myxoid liposarcomas. Oncogene 2014; 33(44): 5201-10.
[] [PMID: 24213580]
Scotto KW. ET-743: More than an innovative mechanism of action. Anticancer Drugs 2002; 13(Suppl. 1): S3-6.
[PMID: 12173491]
Friedman D, Hu Z, Kolb EA, Gorfajn B, Scotto KW. Ecteinascidin-743 inhibits activated but not constitutive transcription. Cancer Res 2002; 62(12): 3377-81.
[PMID: 12067978]
Marco E, García-Nieto R, Mendieta J, Manzanares I, Cuevas C, Gago FA. 3.(ET743)-DNA complex that both resembles an RNA-DNA hybrid and mimicks zinc finger-induced DNA structural distortions. J Med Chem 2002; 45(4): 871-80.
[] [PMID: 11831898]
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]
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, Ceribelli M, Pitarque-Martì M, et al. Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters. Mol Pharmacol 2005; 68(5): 1496-503.
[] [PMID: 15961672]
Feuerhahn S, Giraudon C, Martínez-Díez M, et al. XPF-dependent DNA breaks and RNA polymerase II arrest induced by antitumor DNA interstrand crosslinking-mimetic alkaloids. Chem Biol 2011; 18(8): 988-99.
[] [PMID: 21867914]
Liapis K, Clear A, Owen A, et al. The microenvironment of AIDS-related diffuse large B-cell lymphoma provides insight into the pathophysiology and indicates possible therapeutic strategies. Blood 2013; 122(3): 424-33.
[] [PMID: 23652804]
Haque ASMR, Moriyama M, Kubota K, et al. CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production. Sci Rep 2019; 9(1): 14611.
[] [PMID: 31601953]
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]
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]
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]
Banerjee P, Zhang R, Ivan C, et al. Trabectedin reveals a strategy of immunomodulation in chronic lymphocytic leukemia. Cancer Immunol Res 2019; 7(12): 2036-51.
[] [PMID: 31530560]
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]
Nakamura T, Matsumine A, Sudo A. The value of trabectedin in the treatment of soft tissue sarcoma. Ther Clin Risk Manag 2016; 12: 73-9.
[] [PMID: 26834480]
Karakousis CP, Perez RP. Soft tissue sarcomas in adults. CA Cancer J Clin 1994; 44(4): 200-10.
[] [PMID: 8019927]
van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012; 379(9829): 1879-86.
[] [PMID: 22595799]
Laroche A, Chaire V, Le Loarer F, et al. Activity of trabectedin and the PARP inhibitor rucaparib in soft-tissue sarcomas. J Hematol Oncol 2017; 10(1): 84.
[] [PMID: 28399901]
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]
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]
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]
Petek BJ, Loggers ET, Pollack SM, Jones RL. Trabectedin in soft tissue sarcomas. Mar Drugs 2015; 13(2): 974-83.
[] [PMID: 25686274]
Blay JY, Leahy MG, Nguyen BB, et al. Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. Eur J Cancer 2014; 50(6): 1137-47.
[] [PMID: 24512981]
Blay JY, von Mehren M, Samuels BL, et al. Phase I combination study of trabectedin and doxorubicin in patients with soft-tissue sarcoma. Clin Cancer Res 2008; 14(20): 6656-62.
[] [PMID: 18927308]
Sanfilippo R, Grosso F, Jones RL, et al. Trabectedin in advanced uterine leiomyosarcomas: A retrospective case series analysis from two reference centers. Gynecol Oncol 2011; 123(3): 553-6.
[] [PMID: 21917307]
Gadducci A, Guerrieri ME. Pharmacological treatment for uterine leiomyosarcomas. Expert Opin Pharmacother 2015; 16(3): 335-46.
[] [PMID: 25418060]
Tavella K, Villanucci A, Vannini L, et al. Stable disease in a patient with metastatic leiomyosarcoma treated with trabectedin. Anticancer Drugs 2017; 28(4): 465-8.
[] [PMID: 28181940]
Gadducci A, Grosso F, Scambia G, et al. A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma. Br J Cancer 2018; 119(5): 565-71.
[] [PMID: 30057406]
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]
Pautier P, Floquet A, Chevreau C, et al. 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]
Suarez-Kelly LP, Baldi GG, Gronchi A. Pharmacotherapy for liposarcoma: Current state of the art and emerging systemic treatments. Expert Opin Pharmacother 2019; 20(12): 1503-15.
[] [PMID: 31136210]
Zijoo R, von Mehren M. Efficacy of trabectedin for the treatment of liposarcoma. Expert Opin Pharmacother 2016; 17(14): 1953-62.
[] [PMID: 27615729]
Jones RL, Demetri GD, Schuetze SM, et al. Efficacy and tolerability of trabectedin in elderly patients with sarcoma: Subgroup analysis from a phase III, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Ann Oncol 2018; 29(9): 1995-2002.
[] [PMID: 30084934]
Saponara M, Stacchiotti S, Gronchi A. The safety and efficacy of trabectedin for the treatment of liposarcoma or leiomyosarcoma. Expert Rev Anticancer Ther 2016; 16(5): 473-84.
[] [PMID: 27043847]
Pérez-Losada J, Pintado B, Gutiérrez-Adán A, et al. The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice. Oncogene 2000; 19(20): 2413-22.
[] [PMID: 10828883]
Orvieto E, Furlanetto A, Laurino L, Dei Tos AP. Myxoid and round cell liposarcoma: A spectrum of myxoid adipocytic neoplasia. Semin Diagn Pathol 2001; 18(4): 267-73.
[PMID: 11757867]
Blay JY, Italiano A, Ray-Coquard I, et al. Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: An analysis of 181 patients of the French ATU compassionate use program. BMC Cancer 2013; 13(1): 64.
[] [PMID: 23388156]
Grosso F, Jones RL, Demetri GD, et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: A retrospective study. Lancet Oncol 2007; 8(7): 595-602.
[] [PMID: 17586092]
Assi T, Kattan J, El Rassy E, et al. A comprehensive review of the current evidence for trabectedin in advanced myxoid liposarcoma. Cancer Treat Rev 2019; 72: 37-44.
[] [PMID: 30468937]
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]
Capasso Palmiero U, Morosi L, Bello E, et al. Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin. J Control Release 2018; 276: 140-9.
[] [PMID: 29524443]
Siegel RL, Fedewa SA, Miller KD, et al. Cancer statistics for Hispanics/Latinos, 2015. CA Cancer J Clin 2015; 65(6): 457-80.
[] [PMID: 26375877]
Bhatt A, Glehen O. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer: A review. Indian J Surg Oncol 2016; 7(2): 188-97.
[] [PMID: 27065709]
Pignata S, Cecere SC, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Ann Oncol 2017; 28: viii51-6.
Ray-Coquard I. Biology of ovarian cancer and trabectedin mechanism of action. Future Oncol 2013; 9(12)(Suppl.): 11-7.
[] [PMID: 24195525]
Teplinsky E, Herzog TJ. The efficacy of trabectedin in treating ovarian cancer. Expert Opin Pharmacother 2017; 18(3): 313-23.
[] [PMID: 28140689]
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.
[] [PMID: 15774779]
Del Campo JM, Roszak A, Bidzinski M, et al. 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]
Ferrandina G, Salutari V, Vincenzi B, et al. Trabectedin as single agent in the salvage treatment of heavily treated ovarian cancer patients: A retrospective, multicenter study. Gynecol Oncol 2013; 130(3): 505-10.
[] [PMID: 23774301]
Adam JP, Boumedien F, Letarte N, Provencher D. Single agent trabectedin in heavily pretreated patients with recurrent ovarian cancer. Gynecol Oncol 2017; 147(1): 47-53.
[] [PMID: 28751117]
Monk BJ, Herzog TJ, Wang G, et al. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol 2020; 156(3): 535-44.
[] [PMID: 31924332]
Green AE, Rose PG. Pegylated liposomal doxorubicin in ovarian cancer. Int J Nanomedicine 2006; 1(3): 229-39.
[PMID: 17717964]
Monk BJ, Herzog TJ, Kaye SB, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 2010; 28(19): 3107-14.
[] [PMID: 20516432]
Kaye SB, Colombo N, Monk BJ, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval. Ann Oncol 2011; 22(1): 49-58.
[] [PMID: 20643863]
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]
Pignata S, Scambia G, Villanucci A, et al. A european, observational, prospective trial of trabectedin plus pegylated liposomal doxorubicin in patients with platinum-sensitive ovarian cancer. Oncologist 2021; 26(4): e658-68.
[] [PMID: 33289956]
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]
DeSantis CE, Ma J, Gaudet MM, et al. Breast cancer statistics, 2019. CA Cancer J Clin 2019; 69(6): 438-51.
[] [PMID: 31577379]
Atmaca H, Uzunoglu S. Anti-angiogenic effects of trabectedin (Yondelis; ET-743) on human breast cancer cells. Eur Cytokine Netw 2014; 25(1): 1-7.
[] [PMID: 24941346]
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]
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]
Prakash R, Zhang Y, Feng W, Jasin M. Homologous recombination and human health: The roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb Perspect Biol 2015; 7(4)a016600
[] [PMID: 25833843]
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]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[] [PMID: 33538338]
Gadgeel SM, Stevenson JP, Langer CJ, et al. Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. Lung Cancer 2018; 125: 273-81.
[] [PMID: 30429032]
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]
Studdert AL, Gong CL, Srinivas S, Chin AL, Deresinski S. Application of pharmacoeconomics to formulary management in a health system setting. Am J Health Syst Pharm 2019; 76(6): 381-6.
[] [PMID: 31361838]
Martin-Broto J, Hindi N, Lopez-Pousa A, et al. Assessment of safety and efficacy of combined trabectedin and low-dose radiotherapy for patients with metastatic soft-tissue sarcomas: A nonrandomized phase 1/2 clinical trial. JAMA Oncol 2020; 6(4): 535-41.
[] [PMID: 32077895]
Selle F, Heudel PE, Hardy-Bessard AC, et al. GINECO prospective non-interventional PROSPECTYON study: Trabectedin plus pegylated liposomal doxorubicin for platinum-sensitive recurrent ovarian cancer. Anticancer Res 2020; 40(7): 3939-45.
[] [PMID: 32620635]
Guo Z, Wang H, Meng F, Li J, Zhang S. Combined Trabectedin and anti-PD1 antibody produces a synergistic antitumor effect in a murine model of ovarian cancer. J Transl Med 2015; 13(1): 247.
[] [PMID: 26219551]
Colombo N, Zaccarelli E, Baldoni A, et al. Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer. Br J Cancer 2019; 121(9): 744-50.
[] [PMID: 31537908]
Chu Q, Mita A, Forouzesh B, et al. Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. Clin Cancer Res 2010; 16(9): 2656-65.
[] [PMID: 20406837]
van Waterschoot RA, Eman RM, Wagenaar E, et al. ABCC2, ABCC3, and ABCB1, but not CYP3A, protect against trabectedin-mediated hepatotoxicity. Clin Cancer Res 2009; 15(24): 7616-23.
[] [PMID: 19996204]
Lebedinsky C, Gómez J, Park YC, et al. Trabectedin has a low cardiac risk profile: A comprehensive cardiac safety analysis. Cancer Chemother Pharmacol 2011; 68(5): 1223-31.
[] [PMID: 21416137]
Samuels BL, Chawla S, Patel S, et al. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: Results of a worldwide expanded access program study. Ann Oncol 2013; 24(6): 1703-9.
[] [PMID: 23385197]
Rubio MJ, Lecumberri MJ, Varela S, et al. Efficacy and safety of trabectedin in metastatic uterine leiomyosarcoma: A retrospective multicenter study of the Spanish ovarian cancer research group (GEICO). Gynecol Oncol Rep 2020; 33100594
[] [PMID: 32566719]
Khan T, Gurav P. PhytoNanotechnology: Enhancing delivery of plant based anti-cancer drugs. Front Pharmacol 2018; 8: 1002.
[] [PMID: 29479316]
Loria R, Giliberti C, Bedini A, et al. Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells. J Exp Clin Cancer Res 2019; 38(1): 1.
[] [PMID: 30606223]
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]
Grosso F, Sanfilippo R, Virdis E, et al. Trabectedin in myxoid liposarcomas (MLS): A long-term analysis of a single-institution series. Ann Oncol 2009; 20(8): 1439-44.
[] [PMID: 19465423]
Gronchi A, Bui BN, Bonvalot S, et al. Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma. Ann Oncol 2012; 23(3): 771-6.
[] [PMID: 21642514]
Le Cesne A, Cresta S, Maki RG, et al. A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. Eur J Cancer 2012; 48(16): 3036-44.
[] [PMID: 22749255]
Gronchi A, Ferrari S, Quagliuolo V, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): An international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol 2017; 18(6): 812-22.
[] [PMID: 28499583]
Gronchi A, Hindi N, Cruz J, et al. Trabectedin and radiotherapy in soft tissue sarcoma (TRASTS): Results of a Phase I Study in myxoid liposarcoma from spanish (GEIS), Italian (ISG), French (FSG) sarcoma groups. EClinicalMedicine 2019; 9: 35-43.
[] [PMID: 31143880]
Patel S, von Mehren M, Reed DR, et al. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer 2019; 125(15): 2610-20.
[] [PMID: 31173362]
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]
Nicoletto MO, Baldoni A, Casarin A, et al. Trabectedin plus pegylated liposomal doxorubicin: Retrospective analysis in heavily pretreated platinum-sensitive ovarian cancer. Tumori 2015; 101(5): 506-10.
[] [PMID: 26108247]
Moriceau G, Rivoirard R, Méry B, et al. Real-World outcomes of combination chemotherapy with trabectedin plus pegylated liposomal doxorubicin in patients with recurrent ovarian cancer: A single-center experience. Chemotherapy 2016; 61(3): 122-6.
[] [PMID: 26752402]
Runnebaum IB, Reichert D, Ringsdorf U, et al. Trabectedin plus pegylated liposomal doxorubicin (PLD) for patients with platinum-sensitive recurrent ovarian cancer: A prospective, observational, multicenter study. J Cancer Res Clin Oncol 2018; 144(6): 1185-95.
[] [PMID: 29623421]
Romero I, Mallol P, Santaballa A, et al. Multicenter retrospective study to evaluate the impact of trabectedin plus pegylated liposomal doxorubicin on the subsequent treatment in women with recurrent, platinum-sensitive ovarian cancer. Anticancer Drugs 2019; 30(6): 628-35.
[] [PMID: 31008727]
Cesne AL, Judson I, Maki R, et al. Trabectedin is a feasible treatment for soft tissue sarcoma patients regardless of patient age: A retrospective pooled analysis of five phase II trials. Br J Cancer 2013; 109(7): 1717-24.
[] [PMID: 24022187]
Ploner F, Lamm W, Schur S, et al. The Austrian experience with trabectedin in non-selected patients with metastatic soft tissue sarcoma (STS). J Cancer Res Clin Oncol 2013; 139(8): 1337-42.
[] [PMID: 23666164]
Vincenzi B, Badalamenti G, Armento G, et al. Body mass index as a risk factor for toxicities in patients with advanced soft-tissue sarcoma treated with trabectedin. Oncology 2018; 95(1): 1-7.
[] [PMID: 29510410]
Zelek L, Yovine A, Brain E, et al. A phase II study of yondelis (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer. Br J Cancer 2006; 94(11): 1610-4.
[] [PMID: 16736024]
Goldstein LJ, Gurtler J, Del Prete SA, et al. Trabectedin as a single-agent treatment of advanced breast cancer after anthracycline and taxane treatment: A multicenter, randomized, phase II study comparing 2 administration regimens. Clin Breast Cancer 2014; 14(6): 396-404.
[] [PMID: 25239225]
Sessa C, Cresta S, Noberasco C, et al. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin in solid tumours. Eur J Cancer 2009; 45(12): 2116-22.
[] [PMID: 19419856]

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