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Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group

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Abstract

Objective: This multi-center phase II trial was conducted by the Gynecologic Oncology Group to evaluate the activity and toxicity of irofulven in patients with previously treated adenocarcinoma of the endometrium. Methods: Eligible patients had documented recurrent or persistent endometrial carcinoma after receiving definitive locoregional therapy, and were required to have measurable disease, performance status of 0–2, and adequate bone marrow, hepatic and renal functions prior to study entry. Patients were allowed one prior chemotherapy regimen. The initial dose of irofulven was 11 mg/m2/day for four days administered intravenously. Cycles were repeated every 28 days. Doses were escalated or reduced based on previous cycle toxicity. Results: Twenty-five patients were enrolled onto the trial. There was one (4%) confirmed complete response. Seven (28%) patients had stable disease, with a median duration of 10.4 (range: 4.4–21.6) months. Patients received a median of one (range: 1–5) cycle of protocol treatment. There were three early treatment-related deaths due to renal failure and severe electrolyte disturbances. Two patients experienced grade 4 hematologic adverse effects. Conclusion: Irofulven administered at the dose and schedule used in this trial was minimally active and resulted in significant toxicity.

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References

  1. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ: Cancer Statistics, 2003. CA Cancer J Clin 53: 5–26, 2003

    PubMed  Google Scholar 

  2. Thigpen JT, Buchsbaum HJ, Mangan C, Blessing JA: Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Cancer Treat Rep 63: 21, 1979

    CAS  PubMed  Google Scholar 

  3. Thigpen T, Blessing J, Homesley H, Malfetano J, DiSaia P, Yordan E: Phase III trial of doxorubicin +/-cisplatin in advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group (GOG) study. Proc Am Soc Clin Oncol 12: 261, 1993 (abstract)

    Google Scholar 

  4. Aapro M, Bolis G, Chevallier B, van der Burg MEL, Poveda A, de Oliveira C, Pawinski A, Sahmoud T, Pecorelli S: An EORTC-GCCG randomized phase II trial of doxorubicin (DOX) versus dox-cisplatin (CDDP) in endometrial carcinoma. Proc Am Soc Clin Oncol 13: 275, 1994 (abstract)

    Google Scholar 

  5. Lincoln S, Blessing JA, Lee RB, Rocereto TF: Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 88: 277–281, 2003

    Article  CAS  PubMed  Google Scholar 

  6. Ball HG, Blessing JA, Lentz SS, Mutch DG: A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: A Gynecologic Oncology Group study. Gynecol Oncol 62: 278–281, 1996

    Article  CAS  PubMed  Google Scholar 

  7. Fleming GF, Brunetto VL, Mundt AJ, Burks RT, Look KY, Reid G: Randomized trial of doxorubicin (DOX) plus cisplatin (CIS) versus DOX plus CIS plus paclitaxel (PAX) in patients with advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group (GOG) study. Proc Am Soc Clin Oncol 21: 202a, 2002 (abstr)

    Google Scholar 

  8. McMorris TC: Discovery and development of sesquiterpenoid derived hydroxymethylacylfulvene: A new anticancer drug. Bioorganic & Medicinal Chemistry 7(5): 881–886, 1999

    Google Scholar 

  9. Herzig MC, Arnett B, MacDonald JR, Woynarowski JM: Drug uptake and cellular targets of hydroxy methylacylfulvene (HMAF). Biochem Pharmacol 58: 217–225, 1999

    CAS  PubMed  Google Scholar 

  10. MacDonald JR, Muscoplat CC, Dexter DL, Mangold GL, Chen SF, Kelner MJ, McMorris TC, Von Hoff DD: Preclinical antitumor activity of 6-hydroxymethlacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res 57: 279–283, 1997

    CAS  PubMed  Google Scholar 

  11. Hammond LA, Hilsenbeck SG, Eckhardt SG, Marty J, Mangold G, MacDonald JR, Rowinsky EK, von Hoff DD, Weitman S: Enhanced antitumour activity of 6-hydroxymethylacylfulvene in combination with topotecan or paclitaxel in the MV522 lung carcinoma xenograft model. Eur J Cancer 36: 2430–2436, 2000

    CAS  PubMed  Google Scholar 

  12. Kelner MJ, McMorris TC: Irofulven is synergistic with multiple chemotherapeutic agents. Proc Am Assoc Cancer Res 43: 60, 2002 (abstract)

    Google Scholar 

  13. Investigator’s Brochure, MGI Pharma, Minneapolis, MN, 1998

  14. Eckhardt SG, Baker SD, Britten CD, Hidalgo M, Siu L, Hammond LA, Villalona-Calero MA, Felton S, Drengler R, Kuhn JG, Clark GM, Smith SL, MacDonald JR, Smith C, Moczygemba J, Weitman S, von Hoff DD, Rowinsky EK: Phase I and pharmacokinetic study of irofulven, a novel mushroom-derived cytotoxin, administered for five consecutive days every four weeks in patients with advanced solid malignancies. J Clin Oncol 18(24): 4086–4097, 2000

    CAS  PubMed  Google Scholar 

  15. Thomas JP, Arzoomanian R, Alberti D, Feierabend C, Binger K, Tutsch KD, Steele T, Marnocha R, Smith C, Smith S, MacDonald J, Wilding G, Bailey H: Phase I clinical and pharmacokinetictrial of irofulven. Cancer Chemother Pharmacol 48: 467–472, 2001

    CAS  PubMed  Google Scholar 

  16. Sarosy GA, Kotz H, Smith S, Murgo A, Minasian L, Dyer V, Kohler D, Kim S, Reed E: Phase II study of irofulven in platinum resistant recurrent ovarian cancer. Proc Am Soc Clin Oncol 20: 218a, 2001 (abstract)

    Google Scholar 

  17. Senzer NN, Rakvica R, Chao H, Smith S: A phase II trial of MGI 114 in patients with hormone-refractory prostate cancer. Proc Am Soc Clin Oncol 18: 321a, 1999 (abstract)

    Google Scholar 

  18. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3): 205–216, 2000

    Article  CAS  PubMed  Google Scholar 

  19. Vukelja SJ, Gordon AN, Muscato JJ, Hancock K, Weems G, Smith S, MacDonald J, Herdrich L: Phase II study of irofulven (MGI-114) in platinum (P) and paclitaxel (T) resistant epithelial ovarian cancer (OC). Proc Am Soc Clin Oncol 19: 399a, 2000 (abstract)

    Google Scholar 

  20. Urien S, Alexandre J, Raymond E, Brain E, Smith S, Shah A, Cvitkovic E, Lokiec F: Phase I population pharmacokinetics of irofulven. Anticancer Drugs 14: 353–358, 2003

    CAS  PubMed  Google Scholar 

  21. Berg WJ, Schwartz L, Yu R, Mazumdar M, Motzer RJ: Phase II trial of irofulven (6-ydroxymethylacylfulvene) for patients with advanced renal cell carcinoma. Invest New Drugs 19: 317–320, 2001

    CAS  PubMed  Google Scholar 

  22. Alexandre J, Raymond E, Brain E, Ould Kaci M, Smith S, Misset J-L: Dose-intensity (DI) based escalation phase I study of MGI 114 (irofulven) exploring 3 different i.v. schedules in advanced solid tumors. Ann Oncol 11(4): 138, 2000

    Google Scholar 

  23. Alexandre J, Kahatt C, Ould Kaci M, Raymond E, Brain E, Smith S, Lagree S, Vanderbilt K, Cvitkovic E, Misset JL: Phase I study of irofulven (MGI 114) given as a 5′ infusion once every 2 weeks (W): Preliminary results. Proc Am Soc Clin Oncol 20: 83b, 2001 (abstract)

    Google Scholar 

  24. Jeliffe RW: Creatinine clearance bedside estimate. Ann Intern Med 79: 604, 1973

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111

    Russell J. Schilder

  2. Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, 14263

    John A. Blessing

  3. Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY, 11794

    Michael L. Pearl

  4. Division of Gynecologic Oncology, Case Western Reserve University, Cleveland, OH, 44109

    Peter G. Rose

Authors
  1. Russell J. Schilder
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  2. John A. Blessing
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  3. Michael L. Pearl
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  4. Peter G. Rose
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Schilder, R.J., Blessing, J.A., Pearl, M.L. et al. Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group. Invest New Drugs 22, 343–349 (2004). https://doi.org/10.1023/B:DRUG.0000026262.77502.31

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  • DOI: https://doi.org/10.1023/B:DRUG.0000026262.77502.31

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