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Meta-Analysis
. 2016 Jun 16;11(6):e0157660.
doi: 10.1371/journal.pone.0157660. eCollection 2016.

Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis

Tobias Engel Ayer Botrel  1   2 , Otávio Clark  1   2 , Antônio Carlos Lima Pompeo  2 , Francisco Flávio Horta Bretas  2 , Marcus Vinicius Sadi  2 , Ubirajara Ferreira  2 , Rodolfo Borges Dos Reis  2
Affiliations
Meta-Analysis

Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis

Tobias Engel Ayer Botrel et al. PLoS One. .

Abstract

Objective: Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA) and Western Europe. Androgen-deprivation therapy alone (ADT) remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT) that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel) for metastatic hormone-naive prostate cancer (mHNPC).

Methods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (95% CI).

Results: The final analysis included 3 trials comprising 2,264 patients (mHNPC). Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001), and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). The biochemical progression-free survival (bPFS) also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001), also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%). Finally, the combination of ADT with docetaxel showed a superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%). A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002). In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). Regarding adverse events and severe toxicity (grade ≥3), the group receiving the combined therapy had higher rates of neutropenia, febrile neutropenia and fatigue.

Conclusion: The combination of ADT with docetaxel improved the clinical progression-free survival, bPFS and OS of patients with mHNPC. A superior OS was seen especially for patients with metastatic and high-volume disease. This contemporary combination therapy may now be offered as a first-line treatment for selected patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Trial selection flow.
Fig 2
Fig 2. Comparative effect in clinical progression-free survival of ADT with docetaxel versus ADT alone.
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 3
Fig 3. Comparative effect in biochemical progression-free survival of ADT with docetaxel versus ADT alone.
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 4
Fig 4. Comparative effect in overall survival of ADT with docetaxel versus ADT alone (Fixed-effect model analysis).
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 5
Fig 5. Comparative effect in overall survival of ADT with docetaxel versus ADT alone (random-effects model analysis).
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 6
Fig 6. Comparative effect in overall survival of ADT with docetaxel versus ADT alone in patients with high-volume disease.
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 7
Fig 7. Comparative effect in overall survival of ADT with docetaxel versus ADT alone in patients with low-volume disease.
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 8
Fig 8. Comparative effect in hematologic toxicities of ADT with docetaxel versus ADT alone.
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
Fig 9
Fig 9. Comparative effect in non-hematologic toxicities of ADT with docetaxel versus ADT alone.
Abbreviations: ADT, androgen-deprivation therapy; CI, confidence interval.
See this image and copyright information in PMC

References

    1. http://clinicaltrials.gov/ct2/show/NCT00514540.
    1. Beltran H, Beer TM, Carducci MA, de Bono J, Gleave M, Hussain M, et al. New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol. 2011;60(2):279–90. Epub 2011/05/20. doi: S0302-2838(11)00477-5 [pii] 10.1016/j.eururo.2011.04.038 . - DOI - PubMed
    1. Botrel TE, Clark O, Pompeo AC, Bretas FF, Sadi MV, Ferreira U, et al. Immunotherapy with Sipuleucel-T (APC8015) in patients with metastatic castration-refractory prostate cancer (mCRPC): a systematic review and meta-analysis. International braz j urol: official journal of the Brazilian Society of Urology. 2012;38(6):717–27. Epub 2013/01/11. . - PubMed
    1. Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007;25(12):1596–605. Epub 2007/04/04. doi: JCO.2006.10.1949 [pii] 10.1200/JCO.2006.10.1949 . - DOI - PubMed
    1. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. European urology. 2014;65(2):467–79. Epub 2013/12/11. 10.1016/j.eururo.2013.11.002 . - DOI - PubMed