Skip to main content
SpringerLink
Log in

A phase II trial of irinotecan in hormone-refractory prostate cancer

  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Abstract

Irinotecan is a DNA topoisomerase I inhibitor that has a wide spectrum of activity against human tumors in both preclinical and clinical studies. To evaluate the efficacy of irinotecan in hormone-refractory prostate cancer, we conducted a phase II study in 15 men with metastatic, PSA-progressive disease after primary androgen deprivation. Irinotecan was administered at a dose of 125 mg/m2 weekly for four weeks followed by a two-week rest period; cycles were repeated every six weeks. Response was assessed by evaluation of serial changes in the serum PSA. None of fifteen patients had a decline in PSA of greater than 50%; eight patients had stable disease as a best response. None of three patients with measurable disease had a partial or complete response. Toxicity was primarily hematologic and gastrointestinal, with 40% of patients requiring dose modification due to granulocytopenia and 20% requiring intravenous fluid supplementation after development of diarrhea. There were no treatment-related deaths. We conclude that irinotecan in the dose and schedule used in this trial does not have significant activity against hormone-refractory prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Small EJ, Vogelzang NJ: Second-line hormonal therapy for advanced prostate cancer: A shifting paradigm. J Clin Oncol 15: 382-388, 1997

    PubMed  Google Scholar 

  2. Perry CM, McTavish D: Estramustine phosphate sodium: A review of its pharmacodynamics and pharmacokinetic properties, and therapeutic efficacy in prostate cancer. Drugs Aging 7: 49-74, 1995

    PubMed  Google Scholar 

  3. Small EJ, Marshall ME, Reyno L, Meyers R, Natale R, Meyer M, Lenehan P, Chen L, Eisenberger M: Superiority of suramin + hydrocortisone (S + H) over placebo + hydrocortisone (P + H): Results of a multi-center double-blind phase III study in patients with hormone refractory prostate cancer (HRPC) (abstract). Proc Am Assoc Clin Oncol 17: 308a, 1998

    Google Scholar 

  4. Wasalenko JK, Dawson NA: Management of progressive metastatic prostate cancer. Oncology 11: 1551-1560, 1997

    PubMed  Google Scholar 

  5. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC: Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: A Canadian randomized trial with palliative end points. J Clin Oncol 14: 1756-1764, 1996

    PubMed  Google Scholar 

  6. Hudes GR, Greenberg R, Krigel RL, Fox S, Scher R, Litwin S, Watts P, Speicker L, Tew K, Comis R: Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer. J Clin Oncol 10: 1754- 1761, 1992

    PubMed  Google Scholar 

  7. Pienta KJ, Redman B, Hussain M, Cummings G, Esper PS, Appel C, Flaherty LE: Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate. J Clin Oncol 12: 2005-2012, 1994

    PubMed  Google Scholar 

  8. Hudes GR, Nathan F, Khater C, Haas N, Cornfield M, Giantonio B, Greenberg R, Gomella L, Litwin S, Ross E, Roethke S, McAleer C: Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer. J Clin Oncol 15: 3156-3163, 1997

    PubMed  Google Scholar 

  9. Shelton G, Gerson H, Zuech N, Bagliella E, Benson M, Sawczuk I, Olsson C, Petrylak D: Activity of docetaxel (D) + estramustine (E) after dexamethasone (dex) treatment in patients with androgen insensitive prostate cancer (abstract). Proc Am Soc Clin Oncol 17: 343a, 1998

    Google Scholar 

  10. Hsiang YH, Liu LF: Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res 48: 1722-1726, 1988

    PubMed  Google Scholar 

  11. Kawato Y, Furuta T, Aonuma M: Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. Cancer Chemother Pharmacol 28: 192- 198, 1991

    PubMed  Google Scholar 

  12. Rougier R, Bugart R, Douillard JY, Culine S, Suc E, Brunet P, Becouarn Y, Ychou M, Marty M, Extra JM, Bonneterre J, Adenis A, Seitz JF, Ganem G, Namer M, Conroy T, Negrier S, Merrouche Y, Burki F, Mousseau M, Herait P, Mahjoubi M: Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naïve patients and patients pretreated with flourouracil-based chemotherapy. J Clin Oncol 15: 251-260, 1997

    PubMed  Google Scholar 

  13. Lievano G, Mirochnik Y, Rubenstein M, Shaw M, Guinan P: Antitumor effect of CPT-11, a new derivative of camptothecin, against human prostate cancer (PC-3) in vitroand prostate rat tumor (AT-3) in vivo: Methods Findings Exp Pharmacol 18: 659-662, 1996

    Google Scholar 

  14. Kelly WK, Scher HI, Mazumdar M, Vlamis V, Schwartz M, Fossa SD: Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer. J Clin Oncol 11: 1566-1572, 1993

    PubMed  Google Scholar 

  15. Smith DC, Dunn RL, Strawderman MS, Pienta KJ: Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer. J Clin Oncol 16: 1835-1843, 1998

    PubMed  Google Scholar 

  16. Small EJ, Srinivas S, Egan B, McMillan A, Rearden JP: Doxorubicin and dose-escalated cyclophosphamide with granulocyte colony-stimulating factor for the treatment of hormone-resistant prostate cancer. J Clin Oncol 14: 1617-1625, 1996

    PubMed  Google Scholar 

  17. Sella A, Kilbourn R, Amato R, Bui C, Zukiwski A, Ellerhorst J, Logothetis CJ: Phase II study of ketoconazole combined with weekly doxorubicin in patients with androgen-independent prostate cancer. J Clin Oncol 12: 683-688, 1994

    PubMed  Google Scholar 

  18. Colleoni M, Graiff C, Vicario G, Nelli P, Sgarbossa G, Pancheri F, Manente P: Phase II study of estramustine, oral etoposide, and vinorelbine in hormone-refractory prostate cancer. Am J Clin Oncol 20: 383-386, 1997

    Article  PubMed  Google Scholar 

  19. Fields S, Burris H, Wilding G, Eckardt J, O'Rourke T, Rinaldi D, Snetzer J, Bigley T, Hohneller J, Von Hoff D: Evaluating the role of navelbine in hormone-refractory prostate cancer. Proc Am Soc Clin Oncol 13: 727, 1994

    Google Scholar 

  20. Moore MJ, Osoba D, Murphy K, Tannock IF, Armitage A, Findlay B, Coppin C, Neville A, Venner P, Wilson J: Use of palliative endpoints to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer. J Clin Oncol 12: 689-694, 1994

    PubMed  Google Scholar 

  21. Hudes GR, Kosierowski R, Greenberg R, Ramsey HE, Fox SC, Ozols RF, McAleer CA, Giantonio BJ: Phase II study of topotecan in metastatic hormone-refractory prostate cancer. Invest New Drugs 13: 235-240, 1995

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology-Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA, USA

    David M. Reese, Simon Tchekmedyian, Yvonne Chapman, Diane Prager & Peter J. Rosen

Authors
  1. David M. Reese
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon Tchekmedyian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yvonne Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Diane Prager
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter J. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reese, D.M., Tchekmedyian, S., Chapman, Y. et al. A phase II trial of irinotecan in hormone-refractory prostate cancer. Invest New Drugs 16, 353–359 (1998). https://doi.org/10.1023/A:1006120910380

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006120910380

Search

Navigation