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Drug Evaluation

Preclinical and clinical results with the natural marine product ET-743

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Pages 1843-1853 | Published online: 02 Mar 2005

Bibliography

  • RINEHART KL, HOLT TG, FREGEAU NL et al: Ecteinascidins 729, 743, 745, 759A, 759B, and 770: potent antitumor agents from the Caribbean tunicate Ecteinascidia turbinate. J. Org. Chem. (1990) 55:4512–4515.
  • ••This paper shows that compoundsextracted from tunicates with the structure of ecteinascidins have a potential antitumour activity.
  • GUAN Y, SAKAI R, RINEHART KL, WANG AHJ: Molecular and crystal structures of ecteinascidins: Potent antitumor compounds from the Caribbean tunicate Ecteinascidia turbinate. J. Biomol. Struct. Dpi. (1993) 10:793–818.
  • 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 turbinate. Biochemistry (1996) 35:13303–13309.
  • ••This paper indicates that ET-743 binds tothe N2 position of guanine.
  • MOORE BM 2nd, SEAMAN FC, HURLEY LH: NMR-based model of an ecteinascidin 743-DNA adduct. J. Am. Chem. Soc. (1997) 119:5475–5476.
  • •This paper provided a model indicating a potential interaction between the C unit of ET-743 and nuclear transcription factors.
  • ZEWAIL-FOOTE M, HURLEY LH: Ecteinascidin 743: a minor groove alkylator that bends DNA toward the major groove. J. Med. Chem. (1999) 42:2493–2497.
  • •This paper shows that ET-743 induced DNA structural changes as assessed by NMR spectroscopy.
  • BROGGINI M, PONTI M, OTTOLENGHI S, D'INCALCI M, MONGELLI N, MANTOVANI R: Distamycins inhibit the binding of OTF-1 and NFE-1 transfactors to their conserved DNA elements. Nucleic Acids Res. (1989) 17:1051–1059.
  • BROGGINI M, D'INCALCI M: Modulation of transcription factor-DNA interactions by anticancer drugs. Anti-Cancer Drug Des. (1994) 9:373–387.
  • BONFANTI M, LA VALLE E, FERNANDEZ SOUSA FARO JM, FAIRCLOTH G, CARETTI G, D'INCALCI M: Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anti-Cancer Drug Des. (1999) 14:179–186.
  • ••This is the first paper suggesting that ET-743 could act by interfering with transcription regulation.
  • MINUZZO M, MARCHINI S, BROGGINI M, FAIRCLOTH GT, D'INCALCI M, MANTOVANI R: Interference of transcriptional activation by the anti-neoplastic drug ET-743. Proc. Natl. Acad. Sci. USA (2000) 97:6780–6784.
  • ••This paper shows that exposing cells toET-743 at pharmacologically reasonable concentrations can affect the transcription regulation.
  • JIN S, GORFAJN B, FAIRCLOTH G, SCOTTO KW: Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation. Proc. Natl. Acad. Sci. USA (2000) 97:6775–6779.
  • ••This paper shows that ET-743 can inhibitthe induction of transcription of MDR1.
  • FRIEDMAN D, HU Z, KOLB EA, GORFAJN B, SCOTTO KW: Ecteinascidin-743 inhibits activated but not constitutive transcription. Cancer Res. (2002) 62:3377–3381.
  • •The paper corroborates the idea that ET-743 affects the transcription of activated genes.
  • MARTINEZ EJ, COREY EJ, OWA T: Antitumor activity- and gene expression-based profiling of ecteinascidin ET 743 and phthalascidin PT 650. Chem. Biol. (2001) 146:1–10.
  • ERBA E, BERGAMASCHI D, BASSANO L et al: Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur. Cancer (2001) 37:97–105.
  • ••This paper is the first that shows the cellcycle perturbation induced by ET-743 and the cell cycle phase specificity. It also indicates that NER-deficient cells were less sensitive to ET–743.
  • DAMIA G, SILVESTRI S, CARRASSA L et al: Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathways. Int. I Cancer (2001) 92:583–588.
  • •This paper further demonstrates the relative resistance of NER-deficient cells to ET-743 and characterises the relevance of the other DNA repair mechanisms for the drug sensitivity.
  • ZEWAIL-FOOTE M, LI VS, 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) 8:1033–1049.
  • •This paper indicates that some ET-743-DNA adducts are not efficiently repaired and confirms the relative resistance of NER-deficient cells to ET–743.
  • JIMENO JM, FAIRCLOTH G, CAMERON L et al.: Progress in the acquisition of new marine-derived anticancer compounds: Development of ecteinascidin-743 (ET-743). Drugs Future (1996) 21:1155–1165.
  • •This paper includes a comprehensive review of the preclinical data on ET-743.
  • IZBICKA E, LAWRENCE R, RAYMOND E et al: In vitro antitumor activity of the novel marine agent, ecteinascidin-743 (ET-743, NSC-648766) against human tumors explanted from patients. Ann. Oncol. (1998) 9:981–987.
  • LI WW, TAKAHASHI N, JHANWAR S et al.: Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent. Clin. Cancer Res. (2001) 7:2908–2911.
  • •The paper shows that some tumour cell lines (e.g., STS) are hypersensitive to ET-743.
  • ALBELLA B, FAIRCLOTH G, LOPEZ-LAZARO L, GUZMAN C, JIMENO J, BUEREN JA: In vitro toxicity of ET-743 and aplidine, two marine-derived antineoplastics, on human bone marrow haematopoietic progenitors. comparison with the clinical results. Eur. J. Cancer (2002) 38:1395–1404.
  • VALOTI G, NICOLETTI MI, PELLEGRINO A et al: Ecteinascidin-743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts. Clin. Cancer Res. (1998) 4:1977–1983.
  • ••This paper shows the striking antitumouractivity of ET-743 in ovarian cancer xenografts. These data have prompted clinical investigation of ET-743 in ovarian cancer that has shown a high percentage of response in this human neoplasm.
  • 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) 10:1233–1240.
  • •This paper reports good antitumour activity of ET-743 in several xenografts at doses that were not highly toxic.
  • ERBA E, BERGAMASCHI D, BASSANO L et al: Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to ecteinascidin-743 (ET-743). BE .1 Cancer (2000) 82:1732–1739.
  • TAKEBAYASHI Y, POURQUIER P, ZIMONJIC DB et al: Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat. Med. (2001) 7:961–966.
  • •This paper has confirmed previous fmdings that NER deficiency can confer resistance to ET-743. The paper emphasises the relevance of transcription-coupled NER for drug activity.
  • KANZAKI A, TAKEBAYASHI Y, REN XQ et al: Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743. Mol. Cancer Ther. (2002) 1:1327–1334.
  • SCOTLANDI K, PERDICHIZZI S, MANARA MC et al.: Effectiveness of ecteinascidin-743 against drug-sensitive and -resistant bone tumor cells. Chit. Cancer Res. (2002) 8:3893–3903.
  • •The paper indicates that ET-743 is particularly active in cell lines derived from Ewing's sarcoma and shows that the pattern of resistance is different from that of other drugs. In addition, the paper provides an indication of synergism with other anticancer drugs.
  • TAKAHASHI N, LI WW, BANERJEE D, SCOTTO KW, BERTINO JR: Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells. Clin. Cancer Res. (2001) 7:3251–3257.
  • TAKAHASHI N, LI W, BANERJEE D et al.: Sequence-dependent synergistic cytotoxicity of ecteinascidin-743 and paclitaxel in human breast cancer cell lines in vitro and in vivo. Cancer Res. (2002) 62:6909–6915.
  • •The paper shows sequence-dependent synergism of the combination of ET-743 and paclitaxel, a finding potentially useful to plan clinical investigations with these two drugs.
  • D'INCALCI M, COLOMBO T, UBEZIO P et al.: The combination of yondelis and cisplatin is synergistic against human tumor xenografts. Eur. J. Cancer (2003) 39(13):1920–1926.
  • ••The paper shows that the combination ofET-743 and cisplatin induces antitumour responses in xenografts, which are much greater than each drug alone, without overlapping toxicity.
  • MECO D, COLOMBO T, UBEZIO P et al: Effective combination of ET-743 and doxorubicin in sarcoma: preclinical studies. Cancer Chemother. Pharmacol (2003) 52(2):131–138.
  • MARCHINI S, WEISSBACH L, BONOMI R et al.: Gene expression profile of human chondrosarcoma cell line CS-1 and a variant CS-1 cell line resistant to the marine chemotherapeutic yondelis (ET-743). Proc. AACR-NCIEORTC Conf Molecular Targets Cancer Therapeutics, Boston, MA, USA (2003).
  • BIROCCIO A, GABELLINI C, AMODEI S et al.: Telomere dysfunction increases cisplatin and ecteinascidin-743 sensitivity of melanoma cells. Mol Pharmacol (2003) 63:632–638.
  • •This paper suggests that telomerase dysfunction can enhance the activity of ET-743, providing a rationale to attempt the combination of this drug with telomerase inhibitors.
  • DONALD S, VERSCHOYLE R, GANT TW et al.: High-dose dexamethasone (Dex) protects against the hepatotoxicity of ET-743 in the rat. Eur. Cancer (2002) 38\(Suppl. 7):533.
  • DONALD S, VERSCHOYLE RD, GREAVES P et al.: Complete protection by high-dose dexamethasone against the hepatotoxicity of the novel antitumor drud yondelis (ET-743) in the rat. Cancer Res. (2003) 63(18):5902–5908.
  • ROSING H, HILLEBRAND MJ, JIMENO JM et al.: Analysis of Ecteinascidin 743, a new potent marine-derived anticancer drug, in human plasma by high-performance liquid chromatography in combination with solid-phase extraction. J. Chromatogr. B Biota-led. Sci. Appl. (1998) 710:183–189.
  • ROSING H, HILLEBRAND MJ, JIMENO JM et al.: Quantitative determination of Ecteinascidin 743 in human plasma by miniaturized high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J. Mass Spectrom. (1998) 33:1134–1140.
  • REID JM, KUFFEL MJ, RUBEN SL et al:Rat and human liver cytochrome P450 isoform metabolism of ecteinascidin 743 does not predict gender-dependent toxicity in humans. Clin. Cancer Res. (2002) 8:2952–2962.
  • SPARIDANS RW, ROSING H, HILLEBRAND MJ et al: Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man. Anti-Cancer Drugs (2001) 12:653–666.
  • VERMEIR R, HENDRICKX J, HURKMANS R et al: An interspecies comparison of the metabolism of the anticancer agent ecteinascidin 743. International Conference on CYP P450, Prague, Czech Republic (2003).
  • TAAMMA A, MISSET JL, RIOFRIO M et al.: Phase I and pharmacokinetic study of ecteinascidin-743, a new marine compound, administered as a 24-hour continuous infusion in patients with solid tumors. I Chit. Oncol (2001) 19:1256–1265.
  • •The Phase I study indicates the MTD of ET-743 given as a 24-h infusion and shows that the liver toxicity is reversible and not cumulative. Some responses were also observed.
  • VILLALONA-CALERO MA, ECKHARDT SG, WEISS G et al: A Phase I and pharmacokinetic study of ecteinascidin-743 on a daily x 5 schedule in patients with solid malignancies. Chit. Cancer Res. (2002) 8:75–85.
  • RYAN DP, SUPKO JG, EDER JP et al: Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies. Chit. Cancer Res. (2001) 7:231–242.
  • VAN KESTEREN C, CVITKOVIC E, TAAMMA A et al.: Pharmacokinetics and pharmacodynamics of the novel marine-derived anticancer agent ecteinascidin 743 in a Phase I dose-finding study. Chit. Cancer Res. (2000) 6:4725–4732.
  • TWELVES C, HOEKMAN K, BOWMAN A et al: Phase I and pharmacokinetic study of YondelisTM (Ecteinascidin-743; ET-743) administered as an infusion over lh or 3h every 21 days in patients with solid tumors. Eur. J. Cancer (2003) 39:1842–1851.
  • VAN KESTEREN C, TWELVES C, BOWMAN A et al.: Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a l-and 3-h infusion in a Phase I study. Anti-Cancer Drugs (2002) 13:381–393.
  • FOROUZEH B, HILDAGO M, DENTS L et al: Phase I and pharmacokinetic study of the marine-derived DNA minor groove binder ET-743 on a weekly x3 every-4-week schedule in patients with advanced solid malignancies. Proc. AACR-NCIEORTC Int. Conf. Mol. Targets Cancer Ther. Discov. Biol. Appl, Miami Beach, F1, USA (2001):42.
  • BARUCHEL S, BLANEY S, HERSHON L et al: A Phase I study of ET-743 in pediatric refractory solid tumors: a Children's Oncology Group Study. Proc. Am. Soc. Clin. Oncol. (2002) 21:96a.
  • GOMEZ J, LOPEZ-LAZARO L, GUZMAN C et al: Identification of biochemical parameters that predict the onset of severe toxicities in patients treated with ET-743. Proc. Am. Soc. an. Oncol. (2000) 19:187.
  • LOPEZ-MARTIN JA, NIETO A, DEMETRI GD et al: Safety profile of ecteinascidin-743 (ET-743) in Phase II clinical trials (CT) in adult patients with solid tumors. Proc. Am. Soc. an. Oncol. (2002) 21:96a.
  • ZELEK L, YOVINE A, BRAIN E et al.: Preliminary resultsof phase II study of ecteinascidin-743 (ET-743) with the 24 hour (H) continuous infusion (CI) Q3 weeks schedule in pretreated advanced/ metastatic breast cancer (AMBC) patients (Pts). Proceedings of the I Ith NCTEORTC-AACR Symposium on New Drugs in Cancer Therapy Amsterdam (2000):85.
  • DELALOGE S, YOVINE A, TAAMMA A et al.: Ecteinascidin-743: a marine-derived compound in advanced, pretreated sarcoma patients-preliminary evidence of activity. Clin. Oncol. (2001).
  • •This paper reports the first evidence of activity in advanced pretreated sarcoma patients.
  • DEMETRI GD, MANOLA J, HARMON D et al: Ecteinascidin-743 (ET-743) induces durable responses and promising 1-year survival rates in soft tissue sarcomas (STS): final results of Phase II and pharmacokinetic studies in the USA. Proc. Am. Soc. Clin. Oncol. (2001) 20:352a.
  • LE CESNE A, BLAY J, JUDSON I et al:ET-743 is an active drug in adult soft-tissue sarcoma (STS): a STBSG-EORTC Phase II trial. Proc. Am. Soc. Clin. Oncol. (2001) 20:353a.
  • YOVINE A, RIOFRIO M, BRAIN E et al: Ecteinascidin (ET-743) given as a 24 hour (H) intravenous continous infusion (IVCI) every 3 weeks: results of a Phase II trial in patients (pts) with pretreatment soft tissue sarcomas (PSTS). Proc. Am. Soc. Clin. Oncol. (2001) 20:363a.
  • LOPEZ-MARTIN JA, VERWEIJ J, BLAY J et al: An exploratoryanalysis of tumor growth rate (TGR) variations induced by trabectedin (ecteinascidin-743) in patients (pts) with pretreated advanced soft tissue sarcoma (PASTS). Proc. Am. Soc. Clin. Oncol. (2003):819.
  • VAN GLABBEKE M, VERWEIJ J, JUDSON I, NIELSEN OS: Progression-free rate as the principal end-point for Phase II trials in soft-tissue sarcomas. Eur. Cancer (2002) 38:543–549.
  • DILEO P, CASALI PG, BACCI G et al: Phase II evaluation of 3-hr infusion ET-743 in patients with recurrent sarcomas. Proc. Am. Soc. Clin. Oncol. (2002) 21:408a.
  • GEORGE S, MAKI RG, HARMON D et al: Pase II study of ecteinascidin-743 (ET-743) given by 3-hour IV infusion in patients (pts) with soft tissue sarcomas (STS) failing prior chemotherapies. Proc. Am. Soc. Clin. Oncol. (2002) 21:408a.
  • CASANOVA M, CASALI P, SESSA C et al: Phase II study of 3-hours infusion ecteinascidin-743 (ET-743) in pretreated adult and pediatric patients with advanced or recurrent sarcomas: preliminary results. Proc. Int. Soc. Pediatric Oncol. (2002):257.
  • PARMA G, BAUER J, NOBERASCO C et al: YondelisTM (ET-743, trabectedin) antitumor activity in ovarian cancer patients pretreated with platinum-taxane regimens. Ann. Oncol. (2003) 14\(Suppl. 3):iii52.
  • GRASSELLI G, MALOSSI A, COLOMBO N et al: Phase I and pharmacokinetic (PK) study of ecteinascidin-743 (ET, Trabectedin) and cisplatin (P) combination in pre-treated patients (pts) with selected advanced solid tumors. Proc. Am. Soc. Clin. Oncol. (2003) 22:542.
  • GAJATE C, AN F, MOLLINEDO F: Differential cytostatic and apoptotic effects of ecteinascidin-743 in cancer cells. Transcription-dependent cell cycle arrest and transcription-independent JNK and mitochondrial mediated apoptosis. ./. Biol. Chem. (2002) 277:41580–41589.
  • •This paper indicates that ET-743 at high doses induces apoptosis by transcription-independent mechanisms involving mitochondria.
  • CARDENAL F, RAMIREZ JL, ASTUDILLO J et al.: XPD and RRM1 gene polymorphisms predict gemcitabine (gem)/cisplatin (cis)/docetaxel (doc) outcome in stage III non-small-cell lung cancer (NSCLC): a genetic analysis of the Spanish Lung Cancer Group Phase II trial 9901. Proc. Am. Soc. Clin. Oncol. (2003) 22:649.

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