Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Drug Insight: use of docetaxel in prostate and urothelial cancers

Abstract

Taxanes have emerged as a potent class of chemotherapeutic agents in many malignancies, with two taxanes now in clinical use. Their mechanism of action against tumor cells is by alteration of microtubule dynamics, which causes cell-cycle arrest during mitosis. Docetaxel binds to the microtubules with a higher affinity than paclitaxel, and over a broader range of cell-cycle activities. It has also been shown to promote apoptosis via BCL2 phosphorylation. In hormone-refractory prostate cancer, docetaxel has been studied as both a single agent and in combination with estramustine, and in different treatment schedules, with demonstrated efficacy. Two phase III trials have confirmed a survival benefit, making docetaxel the first chemotherapy agent with proven efficacy against prostate cancer. In urothelial cancer, docetaxel has demonstrated activity and has been investigated as a single agent and in combination regimens. A phase III trial comparing docetaxel and cisplatin to methotrexate, vinblastine, doxorubicin, and cisplatin was inferior when evaluating response rates and overall survival. More recent phase II trials combining docetaxel with two additional agents have shown promise, but confirmatory trials are needed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mechanism of action of docetaxel.
Figure 2: Outcomes of the phase III trials into the use of docetaxel for hormone-refractory prostate cancer.

Similar content being viewed by others

References

  1. Mollinedo F and Gajate C (2003) Microtubules, microtubule-interfering agents and apoptosis. Apoptosis 8: 413–450

    Article  CAS  Google Scholar 

  2. Valiron O et al. (2001) Microtubule dynamics. Cell Mol Life Sci 58: 2069–2084

    Article  CAS  Google Scholar 

  3. Checchi P et al. (2003) Microtubule-interacting drugs for cancer treatment. Trends Pharmacol Sci 24: 361–365

    Article  CAS  Google Scholar 

  4. Mitchison T and Kirschner M (1984) Dynamic instability of microtubule growth. Nature 312: 237–242

    Article  CAS  Google Scholar 

  5. Jordan MA and Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4: 253–265

    Article  CAS  Google Scholar 

  6. Margolis RL and Wilson L (1978) Opposite end assembly and disassembly of microtubules at steady state in vitro. Cell 13: 1–8

    Article  CAS  Google Scholar 

  7. Downing KH (2000) Structural basis for the interaction of tubulin with proteins and drugs that affect microtubule dynamics. Annu Rev Cell Dev Biol 16: 89–111

    Article  CAS  Google Scholar 

  8. Stein CA (1999) Mechanisms of action of taxanes in prostate cancer. Semin Oncol 26 (Suppl 17): 3–7

    CAS  PubMed  Google Scholar 

  9. Haldar S et al. (1997) Bcl2 is the guardian of microtubule integrity. Cancer Res 57: 229–233

    CAS  PubMed  Google Scholar 

  10. Tsujimoto Y and Croce CM (1986) Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A 83: 5214–5218

    Article  CAS  Google Scholar 

  11. Krajewski S et al. (1995) Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res 55: 4471–4478

    CAS  PubMed  Google Scholar 

  12. Apakama I et al. (1996) bcl-2 overexpression combined with p53 protein accumulation correlates with hormone-refractory prostate cancer. Br J Cancer 74: 1258–1262

    Article  CAS  Google Scholar 

  13. Haldar S et al. (1996) Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 56: 1253–1255

    CAS  PubMed  Google Scholar 

  14. Bruno R and Sanderink GJ (1993) Pharmacokinetics and metabolism of Taxotere (docetaxel). Cancer Surv 17: 305–313

    CAS  PubMed  Google Scholar 

  15. Extra JM et al. (1993) Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. Cancer Res 53: 1037–1042

    CAS  PubMed  Google Scholar 

  16. US Food and Drug Administration (online May 2004) Taxotere® (docetaxel) prescribing information. [View PDF] (accessed January 2005)

  17. Picus J and Schultz M (1999) Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results. Semin Oncol 26 (Suppl 17): 14–18

    CAS  PubMed  Google Scholar 

  18. Friedland D et al. (1999) A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2. Semin Oncol 26 (Suppl 17): 19–23

    CAS  PubMed  Google Scholar 

  19. Berry W et al. (2001) Phase II trial of single-agent weekly docetaxel in hormone-refractory, symptomatic, metastatic carcinoma of the prostate. Semin Oncol 28 (Suppl 15): 8–15

    Article  CAS  Google Scholar 

  20. Beer TM et al. (2001) Phase II study of weekly docetaxel in symptomatic androgen-independent prostate cancer. Ann Oncol 12: 1273–1279

    Article  CAS  Google Scholar 

  21. Gravis G et al. (2003) Weekly administration of docetaxel for symptomatic metastatic hormone-refractory prostate carcinoma. Cancer 98: 1627–1634

    Article  CAS  Google Scholar 

  22. Kreis W et al. (1997) Unique synergism or antagonism of combinations of chemotherapeutic and hormonal agents in human prostate cancer cell lines. Br J Urol 79: 196–202

    Article  CAS  Google Scholar 

  23. Petrylak DP et al. (2000) Response and preliminary survival results of a phase II study of docetaxel (D) estramustine (E) in patients with androgen-independent prostate cancer (AIPCA). Proc Am Soc Clin Oncol 19: (abstract 334)

  24. Sinibaldi VJ et al. (2002) Phase II evaluation of docetaxel plus one-day oral estramustine phosphate in the treatment of patients with androgen independent prostate carcinoma. Cancer 94: 1457–1465

    Article  CAS  Google Scholar 

  25. Savarese DM et al. (2001) Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B. J Clin Oncol 19: 2509–2516

    Article  CAS  Google Scholar 

  26. Petrylak DP et al. (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351: 1513–1520

    Article  CAS  Google Scholar 

  27. Tannock IF et al. (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351: 1502–1512

    Article  CAS  Google Scholar 

  28. McCaffrey JA et al. (1997) Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol 15: 1853–1857

    Article  CAS  Google Scholar 

  29. de Wit R et al. (1998) Docetaxel (Taxotere): an active agent in metastatic urothelial cancer; results of a phase II study in non-chemotherapy-pretreated patients. Br J Cancer 78: 1342–1345

    Article  CAS  Google Scholar 

  30. Dimopoulos MA et al. (1998) Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel. Urology 52: 56–60

    Article  CAS  Google Scholar 

  31. Garcia del Muro X et al. (2002) Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer. Br J Cancer 86: 326–330

    Article  CAS  Google Scholar 

  32. Gitlitz BJ et al. (2003) A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma. Cancer 98: 1863–1869

    Article  CAS  Google Scholar 

  33. Dreicer R et al. (2003) Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group. Cancer 97: 2743–2747

    Article  CAS  Google Scholar 

  34. Bamias A et al. (2004) Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. J Clin Oncol 22: 220–228

    Article  CAS  Google Scholar 

  35. Sengelov L et al. (1998) Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study. J Clin Oncol 16: 3392–3397

    Article  CAS  Google Scholar 

  36. von der Maase H et al. (2000) Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 17: 3068–3077

    Article  Google Scholar 

  37. Pectasides D et al. (2000) Chemotherapy with cisplatin, epirubicin and docetaxel in transitional cell urothelial cancer. Phase II trial. Eur J Cancer 36: 74–79

    Article  CAS  Google Scholar 

  38. Pectasides D et al. (2002) Weekly chemotherapy with docetaxel, gemcitabine and cisplatin in advanced transitional cell urothelial cancer: a phase II trial. Ann Oncol 13: 243–250

    Article  CAS  Google Scholar 

  39. National Cancer Institute (online 12 December 2003) Common Terminology Criteria for Adverse Events v3.0. [http://ctep.cancer.gov/reporting/ctc.html] (accessed January 2005)

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenneth J Pienta.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mackler, N., Pienta, K. Drug Insight: use of docetaxel in prostate and urothelial cancers. Nat Rev Urol 2, 92–100 (2005). https://doi.org/10.1038/ncpuro0099

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpuro0099

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing