Investigational New Drugs

, Volume 23, Issue 6, pp 577–581 | Cite as

Phase II study of the efficacy and safety of oral GD0039 in patients with locally advanced or metastatic renal cell carcinoma

  • Philip E. Shaheen
  • Walter Stadler
  • Paul Elson
  • Jennifer Knox
  • Eric Winquist
  • Ronald M. BukowskiEmail author


Seventeen patients with locally advanced or metastatic renal cell carcinoma (RCC) were enrolled in this phase II trial. The purpose of the trial was to assess the efficacy of the administration of oral GD0039, and to further assess the pharmacokinetics and pharmacodynamics of this drug. Patients were given an initial dose of 37.5 μ g/kg b.i.d for 3 weeks followed by one week off in each cycle, with the treatment continuing until disease progression or adverse effects. All 17 patients discontinued treatment due to disease progression or toxicity. Adverse events such as fatigue, nausea and diarrhea were common but generally mild. No evidence of anti-tumor activity of GD0039 was seen in this study.


GD0039 renal cell carcinoma phase II trial 


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  1. 1.
    American Cancer Society. Cited July 28, 2004; available from:
  2. 2.
    Pantuck AJ, Zisman A, Belldegrun AS: The changing natural history of renal cell carcinoma. J Urol 166(5): 1611–1623, 2001CrossRefPubMedGoogle Scholar
  3. 3.
    Bukowski RM: Natural history and therapy of metastatic renal cell carcinoma: The role of interleukin-2. Cancer 80(7): 1198–1220, 1997CrossRefPubMedGoogle Scholar
  4. 4.
    Dennis JW, Laferte S: Tumor cell surface carbohydrate and the metastatic phenotype. Cancer Metastasis Rev 5(3): 185–204, 1987PubMedGoogle Scholar
  5. 5.
    Dennis JW, Laferte S, Waghorne C, Breitman ML, Kerbel RS: Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. Science 236(4801): 582–585, 1987PubMedGoogle Scholar
  6. 6.
    Fernandes B, Sagman U, Auger M, Demetrio M, Dennis JW: Beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. Cancer Res 51(2): 718–723, 1991PubMedGoogle Scholar
  7. 7.
    Olden K, Breton P, Grzegorzewski K, Yasuda Y, Gause BL, Oredipe OA, Newton SA, White SL: The potential importance of swainsonine in therapy for cancers and immunology. Pharmacol Ther 50(3): 285–290, 1991CrossRefPubMedGoogle Scholar
  8. 8.
    Galustian C, Foulds S, Dye JF, Guillou PJ: Swainsonine, a glycosylation inhibitor, enhances both lymphocyte efficacy and tumour susceptibility in LAK and NK cytotoxicity. Immunopharmacology 27(2): 195–172, 1994CrossRefGoogle Scholar
  9. 9.
    Korczak B, Goss P, Fernandez B, Baker M, Dennis JW: Branching N-linked oligosaccharides in breast cancer. Adv Exp Med Biol 353: 95–104, 1994Google Scholar
  10. 10.
    Goss PE, Baker MA, Carver JP, Dennis JW: Inhibitors of carbohydrate processing: A new class of anticancer agents. Clin Cancer Res 1(9): 935–944, 1995PubMedGoogle Scholar
  11. 11.
    Mohla S, White S, Grzegorzewski K, Nielson D, Dunston G, Dickson L, Cha JK, Asseffa A, Olden K: Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms.Google Scholar
  12. 12.
    Goss PE, Reid CL, Bailey D, Dennis JW: Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. Clin Cancer Res 3(7): 1077–1086, 1997PubMedGoogle Scholar
  13. 13.
    Goss PE, Baptiste J, Fernandes B, Baker M, Dennis JW: A phase I study of swainsonine in patients with advanced malignancies. Cancer Res 54(6): 1450–1457, 1994PubMedGoogle Scholar
  14. 14.
    Bjarnason GA, Walde D, Whelan P, Chin J, Batist G: GD0039 in solid tumors. American Society of Clinical Oncology Annual Meeting 2002, abstract # 2494Google Scholar
  15. 15.
    Suzuki O, Nozawa Y, Kawaguchi T, Abe M: Alpha-2, 6-sialylation of L-PHA reactive oligosaccharides and expression of N-acetylglucosaminyltransferase V in human diffuse large B cell lymphoma. Oncol Rep 10(6): 1759–1764, 2003PubMedGoogle Scholar
  16. 16.
    Baptista JA, Goss P, Nghiem M, Krepinsky JJ, Baker M, Dennis JW: Measuring swainsonine in serum of cancer patients: Phase I clinical trial. Clin Chem 40(3): 426–430, 1994PubMedGoogle Scholar
  17. 17.
    World Health Organization Staff. WHO handbook for reporting results of cancer treatment. Geneva, Switzerland: WHO offset publication No 40, 1979Google Scholar
  18. 18.
    Bukowski RM, Novick AC: Clinical practice guidelines: Renal cell carcinoma. Cleve Clin J Med 64 Suppl 1:SI1-44; quiz SI45–7, 1997Google Scholar
  19. 19.
    Kuenen BC, Tabernero J, Baselga J, Cavalli F, Pfanner E, Conte PF, Seeber S, Madhusudan S, Deplanque G, Huisman H, Scigalla P, Hoekman K, Harris AL: Efficacy and toxicity of the angiogenesis inhibitor SU5416 as a single agent in patients with advanced renal cell carcinoma, melanoma, and soft tissue sarcoma. Clin Cancer Res 9(5):1648–1655, 2003.PubMedGoogle Scholar
  20. 20.
    Rowinsky EK, Schwartz GH, Gollob JA, Thompson JA, Vogelzang NJ, Figlin R, Bukowski R, Haas N, Lockbaum P, Li YP, Arends R, Foon KA, Schwab G, Dutcher J: Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell carcinoma. J Clin Oncol 22(15): 3003–3015, 2004CrossRefPubMedGoogle Scholar
  21. 21.
    Motzer RJ, Amato R, Todd M, Hwu WJ, Cohen R, Baselga J, Muss H, Cooper M, Yu R, Ginsberg MS, Needle M: Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma. Invest New Drugs 21(1): 99–101, 2003CrossRefPubMedGoogle Scholar
  22. 22.
    Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA: A randomized trial of bevacizumab, an anti- vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349(5): 427–434, 2003CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Philip E. Shaheen
    • 1
  • Walter Stadler
    • 2
  • Paul Elson
    • 3
  • Jennifer Knox
    • 4
  • Eric Winquist
    • 5
  • Ronald M. Bukowski
    • 1
    • 6
    Email author
  1. 1.Experimental Therapeutics Program, Taussig Cancer CenterCleveland Clinic FoundationUnited States
  2. 2.University of Chicago Medical CenterChicagoUnited States
  3. 3.Biostatistics and Epidemiology, Taussig Cancer CenterCleveland Clinic FoundationClevelandUnited States
  4. 4.Princess Margaret HospitalTorontoCanada
  5. 5.London Health Sciences CenterLondonCanada
  6. 6.Taussig Cancer Center, R33, Cleveland Clinic FoundationClevelandUSA

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