Movatterモバイル変換

[0]ホーム
URL:

Skip to main content
NCBI home page
Search in PMCSearch
As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health.
Learn more:PMC Disclaimer | PMC Copyright Notice
Sarcoma logo

Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas

M von Mehren1,*,S P Balcerzak2,A S Kraft3,J H Edmonson4,S H Okuno4,M Davey1,S Mclaughlin1,M T Beard1,A Rogatko5
1Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
2Ohio State University, OH, USA
3University of Colorado, CO, USA
4Mayo Clinic, Emory University, Atlanta, GA, USA
5Department of Biostatistics, Emory University, Atlanta, GA, USA
✉

*M. von Mehren:m_vonmehren@fccc.edu

Collection date 2004.

Copyright © 2004 Hindawi Publishing Corporation

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PMCID: PMC2395616  PMID:18521404

Abstract

Patients: Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting.

Methods: Dol-10 was given intravenously at a dose of 400 μg/m2 and repeated every 21 days. Toxicities were assessed using the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles to assess response [Miller AB, et al. Cancer 1981; 47(1): 207].

Results: Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significant gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective responses in 12 patients treated with Dol-10.

Discussion: Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced or metastatic soft tissue sarcomas.

Full Text

The Full Text of this article is available as aPDF (57.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bai R., Pettit G. R., Hamel E. Dolastatin 10, a powerful cytostatic peptide derived from a marine animal. Inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain. Biochem Pharmacol. 1990 Jun 15;39(12):1941–1949. doi: 10.1016/0006-2952(90)90613-p. [DOI] [PubMed] [Google Scholar]
  2. Bai R., Roach M. C., Jayaram S. K., Barkoczy J., Pettit G. R., Ludueña R. F., Hamel E. Differential effects of active isomers, segments, and analogs of dolastatin 10 on ligand interactions with tubulin. Correlation with cytotoxicity. Biochem Pharmacol. 1993 Apr 6;45(7):1503–1515. doi: 10.1016/0006-2952(93)90051-w. [DOI] [PubMed] [Google Scholar]
  3. Bai R., Taylor G. F., Cichacz Z. A., Herald C. L., Kepler J. A., Pettit G. R., Hamel E. The spongistatins, potently cytotoxic inhibitors of tubulin polymerization, bind in a distinct region of the vinca domain. Biochemistry. 1995 Aug 1;34(30):9714–9721. doi: 10.1021/bi00030a009. [DOI] [PubMed] [Google Scholar]
  4. Balcerzak S. P., Benedetti J., Weiss G. R., Natale R. B. A phase II trial of paclitaxel in patients with advanced soft tissue sarcomas. A Southwest Oncology Group study. Cancer. 1995 Dec 1;76(11):2248–2252. doi: 10.1002/1097-0142(19951201)76:11<2248::aid-cncr2820761111>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  5. Blay J-Y, van Glabbeke M., Verweij J., van Oosterom A. T., Le Cesne A., Oosterhuis J. W., Judson I., Nielsen O. S. Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy. Eur J Cancer. 2003 Jan;39(1):64–69. doi: 10.1016/s0959-8049(02)00480-x. [DOI] [PubMed] [Google Scholar]
  6. Blay J. Y., Bouhour D., Ray-Coquard I., Dumontet C., Philip T., Biron P. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults. J Clin Oncol. 2000 Nov 1;18(21):3643–3650. doi: 10.1200/JCO.2000.18.21.3643. [DOI] [PubMed] [Google Scholar]
  7. Bokemeyer C., Franzke A., Hartmann J. T., Schöber C., Arseniev L., Metzner B., Link H., Kanz L., Schmoll H. J. A phase I/II study of sequential, dose-escalated, high dose ifosfamide plus doxorubicin with peripheral blood stem cell support for the treatment of patients with advanced soft tissue sarcomas. Cancer. 1997 Oct 1;80(7):1221–1227. [PubMed] [Google Scholar]
  8. Borden E. C., Amato D. A., Edmonson J. H., Ritch P. S., Shiraki M. Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas. Cancer. 1990 Sep 1;66(5):862–867. doi: 10.1002/1097-0142(19900901)66:5<862::aid-cncr2820660509>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  9. Borden E. C., Amato D. A., Rosenbaum C., Enterline H. T., Shiraki M. J., Creech R. H., Lerner H. J., Carbone P. P. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol. 1987 Jun;5(6):840–850. doi: 10.1200/JCO.1987.5.6.840. [DOI] [PubMed] [Google Scholar]
  10. Casper E. S., Christman K. L., Schwartz G. K., Johnson B., Brennan M. F., Bertino J. R. Edatrexate in patients with soft tissue sarcoma. Activity in malignant fibrous histiocytoma. Cancer. 1993 Aug 1;72(3):766–770. doi: 10.1002/1097-0142(19930801)72:3<766::aid-cncr2820720321>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  11. Casper E. S., Cordon-Cardo C., Houghton A. N., Steffens T. A., McCormack P., Magill G. B., Hajdu S. I., Brennan M. F. Biological study of R24 mouse monoclonal antibody in patients undergoing thoracotomy for pulmonary metastases from soft tissue sarcoma. Cancer Invest. 1994;12(1):20–25. doi: 10.3109/07357909409021389. [DOI] [PubMed] [Google Scholar]
  12. Cheson B. D., Zwiebel J. A., Dancey J., Murgo A. Novel therapeutic agents for the treatment of myelodysplastic syndromes. Semin Oncol. 2000 Oct;27(5):560–577. [PubMed] [Google Scholar]
  13. Elias A., Ryan L., Aisner J., Antman K. H. Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma. Semin Oncol. 1990 Apr;17(2 Suppl 4):41–49. [PubMed] [Google Scholar]
  14. Galanis E., Hersh E. M., Stopeck A. T., Gonzalez R., Burch P., Spier C., Akporiaye E. T., Rinehart J. J., Edmonson J., Sobol R. E. Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex: phase I/II experience. J Clin Oncol. 1999 Oct;17(10):3313–3323. doi: 10.1200/JCO.1999.17.10.3313. [DOI] [PubMed] [Google Scholar]
  15. Gold J. E., Masters T. R., Bloom N. D., Shafir M. K., Klein M. J., Kenan S., Osband M. E. Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human soft-tissue sarcoma targets with potentiation by cis-diamminedichloroplatinum(II). J Surg Oncol. 1995 Apr;58(4):212–221. doi: 10.1002/jso.2930580403. [DOI] [PubMed] [Google Scholar]
  16. Hamel E. Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B. Pharmacol Ther. 1992;55(1):31–51. doi: 10.1016/0163-7258(92)90028-x. [DOI] [PubMed] [Google Scholar]
  17. Hoffman Mark A., Blessing John A., Lentz Samuel S., Gynecologic Oncology Group Study A phase II trial of dolastatin-10 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Apr;89(1):95–98. doi: 10.1016/s0090-8258(03)00007-6. [DOI] [PubMed] [Google Scholar]
  18. Kalemkerian G. P., Ou X., Adil M. R., Rosati R., Khoulani M. M., Madan S. K., Pettit G. R. Activity of dolastatin 10 against small-cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification. Cancer Chemother Pharmacol. 1999;43(6):507–515. doi: 10.1007/s002800050931. [DOI] [PubMed] [Google Scholar]
  19. Le Cesne A., Vassal G., Farace F., Spielmann M., Le Chevalier T., Angevin E., Valteau-Couanet D., Fizazi K., Cojean I., Llombard A. Combination interleukin-2 and doxorubicin in advanced adult solid tumors: circumvention of doxorubicin resistance in soft-tissue sarcoma? J Immunother. 1999 May;22(3):268–277. doi: 10.1097/00002371-199905000-00010. [DOI] [PubMed] [Google Scholar]
  20. Licht J. D., Gonin R., Antman K. H. Phase II trial of trimetrexate in patients with advanced soft-tissue sarcoma. Cancer Chemother Pharmacol. 1991;28(3):223–225. doi: 10.1007/BF00685515. [DOI] [PubMed] [Google Scholar]
  21. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  22. O'Bryan R. M., Baker L. H., Gottlieb J. E., Rivkin S. E., Balcerzak S. P., Grumet G. N., Salmon S. E., Moon T. E., Hoogstraten B. Dose response evaluation of adriamycin in human neoplasia. Cancer. 1977 May;39(5):1940–1948. doi: 10.1002/1097-0142(197705)39:5<1940::aid-cncr2820390505>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  23. Omura G. A., Major F. J., Blessing J. A., Sedlacek T. V., Thigpen J. T., Creasman W. T., Zaino R. J. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer. 1983 Aug 15;52(4):626–632. doi: 10.1002/1097-0142(19830815)52:4<626::aid-cncr2820520409>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  24. Pitot H. C., McElroy E. A., Jr, Reid J. M., Windebank A. J., Sloan J. A., Erlichman C., Bagniewski P. G., Walker D. L., Rubin J., Goldberg R. M. Phase I trial of dolastatin-10 (NSC 376128) in patients with advanced solid tumors. Clin Cancer Res. 1999 Mar;5(3):525–531. [PubMed] [Google Scholar]
  25. Plaat B. E., Hollema H., Molenaar W. M., Torn Broers G. H., Pijpe J., Mastik M. F., Hoekstra H. J., van den Berg E., Scheper R. J., van der Graaf W. T. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol. 2000 Sep 15;18(18):3211–3220. doi: 10.1200/JCO.2000.18.18.3211. [DOI] [PubMed] [Google Scholar]
  26. Roché H., Guiochet N., Kerbrat P., Rebattu P., Fargeot P., Cattan A., Armand J. P., Keiling R., Lentz M. A., Van Glabeke M. Phase II trials of tetrahydropyranyl-adriamycin (Pirarubicin) on renal and colon carcinoma, melanoma, and soft tissue sarcoma. Am J Clin Oncol. 1993 Apr;16(2):137–139. doi: 10.1097/00000421-199304000-00011. [DOI] [PubMed] [Google Scholar]
  27. Toppmeyer D. L., Slapak C. A., Croop J., Kufe D. W. Role of P-glycoprotein in dolastatin 10 resistance. Biochem Pharmacol. 1994 Aug 3;48(3):609–612. doi: 10.1016/0006-2952(94)90292-5. [DOI] [PubMed] [Google Scholar]
  28. Van Glabbeke M., Verweij J., Judson I., Nielsen O. S., EORTC Soft Tissue and Bone Sarcoma Group Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002 Mar;38(4):543–549. doi: 10.1016/s0959-8049(01)00398-7. [DOI] [PubMed] [Google Scholar]
  29. Wagener D. J., Somers R., Santoro A., Verweij J., Woll P. J., Blackledge G., Schütte H. J., Lentz M. A., van Glabbeke M. Phase II study of nimustine in metastatic soft tissue sarcoma. European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 1991;27(12):1604–1605. doi: 10.1016/0277-5379(91)90424-c. [DOI] [PubMed] [Google Scholar]
  30. Zalupski M. M., Benedetti J., Balcerzak S. P., Hutchins L. F., Belt R. J., Hantel A., Goodwin J. W. Phase II trial of piroxantrone for advanced or metastatic soft tissue sarcomas. A Southwest Oncology Group study. Invest New Drugs. 1993 Nov;11(4):337–341. doi: 10.1007/BF00874435. [DOI] [PubMed] [Google Scholar]
  31. van Hoesel Q. G., Verweij J., Catimel G., Clavel M., Kerbrat P., van Oosterom A. T., Kerger J., Tursz T., van Glabbeke M., van Pottelsberghe C. Phase II study with docetaxel (Taxotere) in advanced soft tissue sarcomas of the adult. EORTC Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1994 Jul;5(6):539–542. doi: 10.1093/oxfordjournals.annonc.a058909. [DOI] [PubMed] [Google Scholar]

Articles from Sarcoma are provided here courtesy ofWiley

ACTIONS

RESOURCES

[8]ページ先頭
©2009-2025 Movatter.jp