Originally published as JCO Early Release 10.1200/JCO.2009.21.2779 on January 26 2009

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Machiels, J.-P. Search for Related Content PubMed Articles by Machiels, J.-P. Related Articles Related Article Related Correspondence Social Bookmarking                            What's this?

In Reply

Centre du Cancer, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

We thank Oudard et al for pushing the discussion further regarding the utility of adding estramustine phosphate to docetaxel in castration-resistant prostate cancer (CRPC). We agree, as already acknowledged in the discussion of our manuscript, that "our study was not powered to detect a survival advantage."¹ However, Oudard et al suggested that our study was a randomized phase II trial, which was not the case (see statistical methods section in the manuscript).¹ The intention was clearly to perform a comparison between the two arms, and the study was powered to test the assumption that the addition of estramustine to docetaxel would improve the prostate-specific antigen (PSA) response rate.¹

The arguments to support the hypothesis that estramustine, when added to docetaxel, could improve the outcome of CRPC are weak. First, they are mainly based on randomized phase II trials that do not allow reliable comparison between arms, even for PSA response as suggested by Oudard et al.^2,3 Second, in the meta-analysis performed by Fizazi et al,⁴ only a limited number of patients (n = 92) treated with a docetaxel-containing regimen were included. Moreover, all these patients came from the same study where a low PSA response rate was observed in the docetaxel arm: 30% versus 45% in larger TAX 327 phase III trial despite using the same docetaxel regimen (docetaxel 75 mg/m2 every 3 weeks).^2,5 This last point precludes any definitive conclusions regarding the interest of adding estramustine to docetaxel, the only drug that increases survival of patients with CRPC. Finally, indirect comparisons between the Southwest Oncology Group 99-16 and the TAX 327 studies also suggest that docetaxel monotherapy offers similar improvements in survival and PSA response rate as the docetaxel/estramustine combination.^5,6

One of the key messages of our trial is that estramustine phosphate significantly increases toxicity: more patients in the docetaxel/estramustine group (45%) had at least one grade 3/4 toxicity compared with those who received docetaxel alone (21%; P = .005).¹ The increase in toxicity is also suggested by the Fizazi et al⁴ meta-analysis and the indirect comparisons between the Southwest Oncology Group 99-16 and the TAX 327 studies.^5,6 Although, we all believe in what we are doing for the patients with CRPC, we should not forget that we are dealing with palliative patients. These patients are old, with frequent comorbidities. The survival benefit provides by docetaxel remains modest.^5,6 "Primum non nocere" is one of the most important principle of antic and modern medicine, particularly in the case of palliative disease. In this context, we strongly believe that estramustine should not be used in combination with chemotherapy, based on the available data. Only a large randomized trial including several hundreds of patients could, maybe, show a small clinical benefit in favor of estramustine-based chemotherapy. Would it be relevant in regard of the quality of life of our patients?

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Machiels JP, Mazzeo F, Clausse M: Prospective randomized study comparing docetaxel, estramustine, prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer. J Clin Oncol 26:5261–5268, 2008.[Abstract/Free Full Text]

2. Eymard JC, Priou F, Zannetti A, et al: Randomized phase II study of docetaxel plus estramustine and single-agent docetaxel in patients with metastatic hormone-refractory prostate cancer. Ann Oncol 18:1064–1070, 2007.[Abstract/Free Full Text]

3. Caffo O, Sava T, Comploj E, et al: Docetaxel and estramustine as first-line chemotherapy for patients with hormone-refractory advanced prostate cancer: Final results of a multicentric phase II randomized trial. J Clin Oncol 25:18s; 2007 (suppl) abstr 15552.

4. Fizazi K, Le Maitre A, Hudes G, et al: Meta-analysis of estramustine in prostate cancer (MECaP) Trialists' Collaborative Group: Addition of estramustine to chemotherapy and survival of patients with castration-refractory prostate cancer—A meta-analysis of individual patient data. Lancet Oncol 8:994–1000, 2007.[CrossRef][Medline]

5. Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 35:1502–1512, 2004.

6. Petrylak DP, Tangen CM, Hussain MH, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced prostate cancer. N Engl J Med 35:1513–1520, 2004.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

• Combining Docetaxel With Estramustine: Back to the Future?
  Stéphane Oudard, Jean Christophe Eymard, and Karim Fizazi
  JCO 2009 27: 1148-1149 [Full Text]

Related Correspondence

• Combining Docetaxel With Estramustine: Back to the Future?
  Stéphane Oudard, Jean Christophe Eymard, and Karim Fizazi
  JCO 2009 27: 1148-1149 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Machiels, J.-P. Search for Related Content PubMed Articles by Machiels, J.-P. Related Articles Related Article Related Correspondence Social Bookmarking                            What's this?