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Investigational New Drugs

, Volume 19, Issue 4, pp 317–320 | Cite as

Phase II Trial of Irofulven (6-Hydroxymethylacylfulvene) for Patients with Advanced Renal Cell Carcinoma

  • William J. Berg
  • Lawrence Schwartz
  • Richard Yu
  • Madhu Mazumdar
  • Robert J. Motzer
Article

Abstract

The aim of this study was to determine the antitumor activityof irofulven (6-hydroxymethylacylfulvene) in patients withadvanced renal cell carcinoma (RCC). Eligible patients hadadvanced renal cell carcinoma with bidimensionally measurabledisease, a Karnofsky performance status of at least 70, lifeexpectancy of greater than three months, no prior treatmentwith chemotherapy, and no evidence of brain metastases.Irofulven was administered at a dose of 11 mg/m2 by 5-minintravenous infusion, on 5 consecutive days. Cycles wererepeated every 28 days. Thirteen patients were enrolled inthis study and 12 were evaluable for response. Of the twelveevaluable patients, no major responses were achieved. Eightpatients had stable disease as best response. Toxicityincluded myelosuppression and gastrointestinal side effects.At the dose and schedule used in this trial, irofulven did notproduce clinical response in RCC.

advanced renal cell carcinoma irofulven Phase II trial 

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REFERENCES

  1. 1.
    Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 50: 7–33, 2000Google Scholar
  2. 2.
    Motzer RJ, Bander NH, Nanus DM: Renal-cell carcinoma. N Engl J Med 335: 865–875, 1996Google Scholar
  3. 3.
    Gleave ME, Elhilali M, Fradet Y, Davis I, Venner P, Saad F, Klotz LH, Moore MJ, Paton V, Bajamonde A, Group TCUO: Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. N Engl J Med 338: 1265–1271, 1998Google Scholar
  4. 4.
    Negrier S, Escudier B, Lasset C, Douillard J-Y, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T, d'Immunotherapie TGF: Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N EngI J Med 338: 1272–1278, 1998Google Scholar
  5. 5.
    Motzer RJ, Vogelzang NJ: Chemotherapy for renal cell carcinoma. In: Raghaven D, Scher HI, Leibel SA, Lange P (eds) Principles and Practice of Genitourinary Oncology. Lippincott Raven, Philadelphia, 1997, pp 885–896Google Scholar
  6. 6.
    Yagoda A, Petrylak D, Thompson S: Cytotoxic chemotherapy for advanced renal cell carcinoma. Urol Clin of N Am 20: 303–321, 1993Google Scholar
  7. 7.
    Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J: Survival and Prognostic Stratification of 670 Patients with Advanced Renal Cell Carcinoma. J Clin Oncol 17: 2530–2540, 1999Google Scholar
  8. 8.
    Herzig MCS, Arnett B, Mac Donald JR, Woynarowski JM: Drug uptake and cellular targets of hydroxymethylacylfulvene (HMAF). Biochem Pharmacol 58: 217–225, 1999Google Scholar
  9. 9.
    Woynarowski JM, Napier C, Koester SK, Chen S-F, Troyer D, Chapman W, MacDonald JR: Effects on DNA integrity and apoptosis induction by a novel antitumor sesquiterpene drug, 6-hydroxymethylacylfulvene (HMAF, MGI 114). Biochem Pharmacol 54: 1181–1193, 1997Google Scholar
  10. 10.
    Izbecka E, Davidson K, Lawrence R, Cote R, MacDonald JR, Von Hoff DD: Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression. Anticancer Res 19: 1299–1307, 1999Google Scholar
  11. 11.
    MacDonald JR, Muscoplat CC, Dexter DL, Mangold GL, Chen SF, Kelner MJ, McMorris TC, Von Hoff DD: Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res 57: 279–283, 1997Google Scholar
  12. 12.
    Izbicka E, Lawrence R, Davidson K, Cerna C, Gomez L, Mac-Donald JR, Weitman S, Von Hoff DD: Anticancer activity of MGI 114 against human tumor specimens taken directly from adult and pediatric patients. (Abstract) Proceedings of the 10th NCI-EORTC Symposium on New Drugs in Cancer Therapy 10: 17, 1998Google Scholar
  13. 13.
    Kelner NU, McMorris TC, Estes L, Samson KM, Bagnell RD, Taetle R: Efficacy of MGI 114 (6-hydroxymethylacylfulvene, HMAF) against the mdr1/gp170 metastatic MV 522 lung carcinoma xenograft. Eur J Cancer 34: 908–913, 1998Google Scholar
  14. 14.
    Eckhardt SG, Baker SD, Wiess GR, Kraynak M, Britten C, Siu L, MacDonald JR, Smith S, De Moor C, Moczygemba J, Von Hoff DD, Rowinsky EK: A phase I and pharmacokinetic study of the novel mushroom-derived cytotoxin, MGI 114, in patients with advanced cancer. (Abstract) Proc Amer Soc Oncol 17: 233a, 1998Google Scholar
  15. 15.
    Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 47: 207–214, 1981Google Scholar
  16. 16.
    Simon R: Optimal two-stage designs for phase II clinical trials. Controlled Clinical Trials 10: 1–10, 1989Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • William J. Berg
    • 1
    • 2
  • Lawrence Schwartz
    • 3
  • Richard Yu
    • 1
  • Madhu Mazumdar
    • 4
  • Robert J. Motzer
    • 1
    • 2
  1. 1.Division of Solid Tumor Oncology, Department of MedicineGenitoury Oncology ServiceUSA
  2. 2.Department of MedicineCornell University Medical CollegeNew YorkU.S.A.
  3. 3.Department of RadiologyMemorial Sloan-Kettering Cancer CenterUSA
  4. 4.Department of Biostatistics and EpidemiologyMemorial Sloan-Kettering Cancer CenterUSA

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