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.

  • Original Article
  • Published:

Clinical Research

Are post-docetaxel treatments effective in patients with castration-resistant prostate cancer and performance of 2? A meta-analysis of published trials

Prostate Cancer and Prostatic Diseases volume 16, pages 323–327 (2013)Cite this article

Subjects

Abstract

Background:

About 20% of patients with prostate cancer have an ECOG performance status (PS) ⩾2 at diagnosis. We investigate if current treatment options for castration-resistant prostate cancer (CRPC) may decrease the risk of death even in patients with ECOG PS of 2.

Methods:

PubMed was reviewed for phase III randomized trials in patients with CRPC progressed after docetaxel chemotherapy. Characteristics of each study and the relative hazard ratio (HR) for overall survival and 95% confidence interval (CI) were collected. Summary HR was calculated using random- or fixed-effects models depending on the heterogeneity of included studies.

Results:

A total of 3,149 patients was available for meta-analysis. In the overall population, the experimental treatments decrease the risk of death by 31% (HR=0.69; 95% CI: 0.63–0.76; P<0.001). The activity of experimental treatments was similar in 2,859 patients with ECOG-PS=0 or 1 with a reduced risk of death of 31% (HR=0.69; 95% CI: 0.62–0.76). A total of 290 patients (9.2%) had ECOG-PS=2 and experimental treatments decreased the risk of death by 26% (HR=0.74; 95% CI: 0.56–0.98; P=0.035) compared with the controls even in this sub-group. When patients were stratified by type of treatment, the reduction of the risk of death was confirmed for hormonal therapies: abiraterone and enzalutamide (HR=0.72; 95% CI: 0.52–0.99; P=0.046), but not for chemotherapy (HR=0.81; 95% CI: 0.48–1.37; P=0.43).

Conclusions:

We believe this is the first study reporting a benefit in second-line setting for CRPC patients previously treated with docetaxel and poor PS.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. American Cancer Society. Cancer Facts & Figures 2012 American Cancer Society: Atlanta, Georgia, USA.

  2. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351: 1502–1512.

    Article  CAS  Google Scholar 

  3. Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351: 1513–1520.

    CAS  PubMed  Google Scholar 

  4. Altavilla A, Iacovelli R, Procopio G, Alesini D, Risi E, Campennì GM et al. Medical strategies for treatment of castration resistant prostate cancer (CRPC) docetaxel resistant. Cancer Biol Ther 2012; 13: 1001–1008.

    Article  CAS  Google Scholar 

  5. Paoli CJ, Bach BA, Tsai KT, Wong B . A retrospective study of performance status in oncology patients at diagnosis and over the first year in routine clinical practice. J Clin Oncol 2011; 29, (suppl; abstr e16521).

  6. Oosterlinck W, Mattelaer J, Derde MP, Kaufman L . Prognostic factors in advanced prostatic carcinoma treated with total androgen blockade. Flutamide with orchiectomy or with LHRH analogues. A Belgian multicentric study of 546 patients. Acta Urol Belg 1995; 63: 1–9.

    CAS  PubMed  Google Scholar 

  7. Halabi S, Vogelzang NJ, Kornblith AB, Ou SS, Kantoff PW, Dawson NA, Small EJ . Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol 2008; 26: 2544–2549.

    Article  Google Scholar 

  8. Omlin A, Pezaro C, Mukherji D, Mulick Cassidy A, Sandhu S, Bianchini D et al. Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms. Eur Urol 2013; 64: 300–306.

    Article  Google Scholar 

  9. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP . Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649–655.

    Article  CAS  Google Scholar 

  10. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ . Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17: 1–12.

    Article  CAS  Google Scholar 

  11. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.

    Article  Google Scholar 

  12. Morris JA, Gardner MJ . Calculating confidence intervals for relative risks (odds ratios) and standardised ratios and rates. Br Med J 1988; 296: 1313–1316.

    Article  CAS  Google Scholar 

  13. Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.

    Article  Google Scholar 

  14. Der Simonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

    Article  CAS  Google Scholar 

  15. Begg CB, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088–1101.

    Article  CAS  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

    Article  CAS  Google Scholar 

  17. Review Manager (RevMan) [Computer program]. Version 5.2. The Nordic Cochrane Centre. The Cochrane Collaboration. Copenhagen, 2012.

  18. Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol 2009; 27: 5431–5438.

    Article  CAS  Google Scholar 

  19. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010; 376: 1147–1154.

    Article  CAS  Google Scholar 

  20. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012; 13: 983–992.

    Article  CAS  Google Scholar 

  21. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012; 367: 1187–1197.

    Article  CAS  Google Scholar 

  22. Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R et al. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: The CAPPA-2 study. Lung Cancer 2013; 81: 77–83.

    Article  Google Scholar 

  23. Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN et al. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol 2013; (Epub ahead of print).

  24. Jouveshomme S, Canoui-Poitrine F, Le Thuaut A, Bastuji-Garin S . Results of platinum-based chemotherapy in unselected performance status (PS) 2 patients with advanced non-small cell lung cancer: a cohort study. Med Oncol 2013; 30: 544–553.

    Article  Google Scholar 

  25. National Comprehensive Cancer Network. Prostate Cancer. http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. . Accessed on 20 January 2012.

  26. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368: 138–148.

    Article  CAS  Google Scholar 

  27. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995–2005.

    Article  CAS  Google Scholar 

  28. Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol 2012; 13: 1210–1217.

    Article  CAS  Google Scholar 

  29. Sternberg CN, Molina A, North S, Mainwaring P, Fizazi K, Hao Y et al. Effect of abiraterone acetate on fatigue in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy. Ann Oncol 2012; 24 (4): 1017–1025.

    Article  Google Scholar 

  30. Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol 1999; 17: 2506–2513.

    Article  CAS  Google Scholar 

  31. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormoneresistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996; 14: 1756–1764.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Oncology and Human Pathology, Oncology Unit B, Sapienza University of Rome, Rome, Italy

    R Iacovelli, A Altavilla & E Cortesi

  2. Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit 1, Milan, Italy

    G Procopio

  3. Azienda Sanitaria USL 8, Medical Oncology Unit, Arezzo, Italy

    S Bracarda

  4. Department of Medical Oncology, Polytechnic University of the Marche Region, Ancona, Italy

    M Santoni & S Cascinu

Authors
  1. R Iacovelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Altavilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Procopio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Bracarda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Santoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Cascinu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Cortesi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R Iacovelli.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iacovelli, R., Altavilla, A., Procopio, G. et al. Are post-docetaxel treatments effective in patients with castration-resistant prostate cancer and performance of 2? A meta-analysis of published trials. Prostate Cancer Prostatic Dis 16, 323–327 (2013). https://doi.org/10.1038/pcan.2013.20

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2013.20

Keywords

This article is cited by

Search

Advanced search

Quick links