Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (54)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Hendriks, H. R.
Right arrow Articles by Faircloth, G. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hendriks, H. R.
Right arrow Articles by Faircloth, G. T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Annals of Oncology 10:1233-1240, 1999
© 1999 European Society for Medical Oncology

research-article

High antitumour activity of ET743 against human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer

H. R. Hendriks1,, H. H. Fiebig2, R. Giavazzi3, S. P. Langdon4, J. M. Jimeno5 and G. T. Faircloth6

1NDDO Oncology, University Hospital Vrije Universiteit Amsterdam, The Netherlands
2Tumor Biology Center, University of Freiburg, Freiburg im Breisgau Germany
3Mario Negri Institute Bergamo, Italy
4ICRF Medical Oncology Unit, Western General Hospital Edinburgh, UK
5PharmaMar S.A., Research and Development, Tres Cantos (Madrid) Spain
6PharmaMar USA Inc. Cambridge, MA, USA

Correspondence to: H. R. Hendriks, MD NDDO Oncology, University Hospital Vrije Universiteit, Amstelveenseweg 601, 1081 JC Amsterdam, The Netherlands E-mail: hr.hendriks{at}planet.nl

Background: Ecteinascidin-743 (ET743) is a novel antitumour agent originating from the Caribbean tunicate Ecteinascidia turbinata. It has potent cytotoxic and antitumour activity and a potential new mechanism of action. The aim of the present study was to further explore the antitumour activity of ET743 in human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer.

Design: As the antitumour profile of ET743 was largely unknown a chemo-sensitive and a marginal chemo-resistant human tumour xenograft were selected for each tumour type. ET743 was administered intravenously using two administration schedules (days 0, 4, 8 and 0–2,13–15).

Results: ET743 was very active at the maximum tolerated dose (MTD) in the chemo-sensitive xenograft melanoma MEXF 989, non-small-cell lung cancer LXFL 529, and ovarian cancers HOC22 and (marginally resistant to cisplatin) HOC18. Activity was also seen at 1/2 MTD. Apart from HOC18, ET743 caused complete remissions in the responding xenografts. The compound was inactive in the chemo-resistant xenograft melanoma MEXF 514 and non-small-cell lung cancer LXFA 629. In terms of antitumour activity the days 0, 4, 8 schedule had advantages over the days 0–2,13–15 schedule.

Conclusions: ET743 is a very effective agent in chemo-sensitive and marginal chemo-resistant xenografts, but inactive in chemo-resistant tumour xenografts. The activity of ET743 in the marginally cisplatin-resistant ovarian cancer HOC18 might indicate absence or incomplete cross-resistance against cisplatin. It is recommended to include melanoma, non-small-cell lung cancer, and ovarian cancer in phase II clinical trials and to use an intermittent schedule.

antitumour activity, ET743, human tumour xenografts, melanoma, non-small-cell lung cancer, ovarian cancer


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Ann OncolHome page
M. von Mehren, R. J. Schilder, J. D. Cheng, E. Temmer, T. M. Cardoso, F. G. Renshaw, E. Bayever, P. Zannikos, Z. Yuan, and R. B. Cohen
A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies
Ann. Onc., October 1, 2008; 19(10): 1802 - 1809.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M. Biscardi, R. Caporale, F. Balestri, S. Gavazzi, J. Jimeno, and A. Grossi
VEGF inhibition and cytotoxic effect of aplidin in leukemia cell lines and cells from acute myeloid leukemia
Ann. Onc., October 1, 2005; 16(10): 1667 - 1674.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. Garcia-Carbonero, J.G. Supko, R.G. Maki, J. Manola, D.P. Ryan, D. Harmon, T.A. Puchalski, G. Goss, M.V. Seiden, A. Waxman, et al.
Ecteinascidin-743 (ET-743) for Chemotherapy-Naive Patients With Advanced Soft Tissue Sarcomas: Multicenter Phase II and Pharmacokinetic Study
J. Clin. Oncol., August 20, 2005; 23(24): 5484 - 5492.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. Martinez, M. Sanchez-Beato, A. Carnero, V. Moneo, J. C. Tercero, I. Fernandez, M. Navarrete, J. Jimeno, and M. A. Piris
Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naive patients
Mol. Cancer Ther., May 1, 2005; 4(5): 814 - 823.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Allavena, M. Signorelli, M. Chieppa, E. Erba, G. Bianchi, F. Marchesi, C. O. Olimpio, C. Bonardi, A. Garbi, A. Lissoni, et al.
Anti-inflammatory Properties of the Novel Antitumor Agent Yondelis (Trabectedin): Inhibition of Macrophage Differentiation and Cytokine Production
Cancer Res., April 1, 2005; 65(7): 2964 - 2971.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Lau, J. G. Supko, S. Blaney, L. Hershon, N. Seibel, M. Krailo, W. Qu, D. Malkin, J. Jimeno, M. Bernstein, et al.
A Phase I and Pharmacokinetic Study of Ecteinascidin-743 (Yondelis) in Children with Refractory Solid Tumors. A Children's Oncology Group Study
Clin. Cancer Res., January 15, 2005; 11(2): 672 - 677.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. Garcia-Carbonero, J.G. Supko, J. Manola, M.V. Seiden, D. Harmon, D.P. Ryan, M.T. Quigley, P. Merriam, J. Canniff, G. Goss, et al.
Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients With Progressive Sarcomas of Soft Tissues Refractory to Chemotherapy
J. Clin. Oncol., April 15, 2004; 22(8): 1480 - 1490.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M. L. Amador, J. Jimeno, L. Paz-Ares, H. Cortes-Funes, and M. Hidalgo
Progress in the development and acquisition of anticancer agents from marine sources
Ann. Onc., November 1, 2003; 14(11): 1607 - 1615.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Donald, R. D. Verschoyle, P. Greaves, T. W. Gant, T. Colombo, M. Zaffaroni, R. Frapolli, M. Zucchetti, M. D'Incalci, D. Meco, et al.
Complete Protection by High-Dose Dexamethasone against the Hepatotoxicity of the Novel Antitumor Drug Yondelis (ET-743) in the Rat
Cancer Res., September 15, 2003; 63(18): 5902 - 5908.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Takahashi, W. Li, D. Banerjee, Y. Guan, Y. Wada-Takahashi, M. F. Brennan, T.-C. Chou, K. W. Scotto, and J. R. Bertino
Sequence-dependent Synergistic Cytotoxicity of Ecteinascidin-743 and Paclitaxel in Human Breast Cancer Cell Lines in Vitro and in Vivo
Cancer Res., December 1, 2002; 62(23): 6909 - 6915.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Scotlandi, S. Perdichizzi, M. C. Manara, M. Serra, S. Benini, V. Cerisano, R. Strammiello, M. Mercuri, G. Reverter-Branchat, G. Faircloth, et al.
Effectiveness of Ecteinascidin-743 against Drug-sensitive and -resistant Bone Tumor Cells
Clin. Cancer Res., December 1, 2002; 8(12): 3893 - 3903.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Gajate, F. An, and F. Mollinedo
Differential Cytostatic and Apoptotic Effects of Ecteinascidin-743 in Cancer Cells. TRANSCRIPTION-DEPENDENT CELL CYCLE ARREST AND TRANSCRIPTION-INDEPENDENT JNK AND MITOCHONDRIAL MEDIATED APOPTOSIS
J. Biol. Chem., October 25, 2002; 277(44): 41580 - 41589.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Donald, R. D. Verschoyle, R. Edwards, D. J. Judah, R. Davies, J. Riley, D. Dinsdale, L. L. Lazaro, A. G. Smith, T. W. Gant, et al.
Hepatobiliary Damage and Changes in Hepatic Gene Expression Caused by the Antitumor Drug Ecteinascidin-743 (ET-743) in the Female Rat
Cancer Res., August 1, 2002; 62(15): 4256 - 4262.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
B. A. Chabner
Cytotoxic Agents in the Era of Molecular Targets and Genomics
Oncologist, August 1, 2002; 7(90003): 34 - 41.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. A. Villalona-Calero, S. G. Eckhardt, G. Weiss, M. Hidalgo, J. H. Beijnen, C. van Kesteren, H. Rosing, E. Campbell, M. Kraynak, L. Lopez-Lazaro, et al.
A Phase I and Pharmacokinetic Study of Ecteinascidin-743 on a Daily x 5 Schedule in Patients with Solid Malignancies
Clin. Cancer Res., January 1, 2002; 8(1): 75 - 85.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Takahashi, W. W. Li, D. Banerjee, K. W. Scotto, and J. R. Bertino
Sequence-dependent Enhancement of Cytotoxicity Produced by Ecteinascidin 743 (ET-743) with Doxorubicin or Paclitaxel in Soft Tissue Sarcoma Cells
Clin. Cancer Res., October 1, 2001; 7(10): 3251 - 3257.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Delaloge, A. Yovine, A. Taamma, M. Riofrio, E. Brain, E. Raymond, P. Cottu, F. Goldwasser, J. Jimeno, J. L. Misset, et al.
Ecteinascidin-743: A Marine-Derived Compound in Advanced, Pretreated Sarcoma Patients--Preliminary Evidence of Activity
J. Clin. Oncol., March 1, 2001; 19(5): 1248 - 1255.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. Taamma, J. L. Misset, M. Riofrio, C. Guzman, E. Brain, L. Lopez Lazaro, H. Rosing, J. M. Jimeno, and E. Cvitkovic
Phase I and Pharmacokinetic Study of Ecteinascidin-743, a New Marine Compound, Administered as a 24-hour Continuous Infusion in Patients With Solid Tumors
J. Clin. Oncol., March 1, 2001; 19(5): 1256 - 1265.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. P. Ryan, J. G. Supko, J. P. Eder, M. V. Seiden, G. Demetri, T. J. Lynch, A. J. Fischman, J. Davis, J. Jimeno, and J. W. Clark
Phase I and Pharmacokinetic Study of Ecteinascidin 743 Administered as a 72-Hour Continuous Intravenous Infusion in Patients with Solid Malignancies
Clin. Cancer Res., February 1, 2001; 7(2): 231 - 242.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
Y. Takebayashi, F. Goldwasser, Y. Urasaki, G. Kohlhagen, and Y. Pommier
Ecteinascidin 743 Induces Protein-linked DNA Breaks in Human Colon Carcinoma HCT116 Cells and Is Cytotoxic Independently of Topoisomerase I Expression
Clin. Cancer Res., January 1, 2001; 7(1): 185 - 191.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
C. van Kesteren, E. Cvitkovic, A. Taamma, L. López-Lázaro, J. M. Jimeno, C. Guzman, R. A. A. Mathôt, J. H. M. Schellens, J.-L. Misset, E. Brain, et al.
Pharmacokinetics and Pharmacodynamics of the Novel Marine-derived Anticancer Agent Ecteinascidin 743 in a Phase I Dose-finding Study
Clin. Cancer Res., December 1, 2000; 6(12): 4725 - 4732.
[Abstract] [Full Text]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.