Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

Amanda Breakey, Mercer University College of Pharmacy

The American Cancer Society states that common androgen-deprivation therapy (ADT) used in the treatment of prostate cancer includes orchiectomy, luteinizing hormone-releasing hormone (LHRH) agonists, and LHRH antagonists.1 According to The National Cancer Institute, in men with metastatic prostate cancer hormone therapy alone is the standard of care. However, authors also state that many prostate cancers that initially respond to hormone therapy eventually stop responding, also known as hormone- or castration-resistant prostate cancer. In men that develop castration-resistant disease, it is stated that one of the treatment regimens includes chemotherapy, most commonly with the drug docetaxel.2

According the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines, continuous ADT is recommended as first-line treatment of metastatic, hormone-naïve prostate cancer. The guidelines also recommend that ADT plus docetaxel be used as first-line treatment in these men that are fit enough to receive chemotherapy.3

Title: Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer4
Design Randomized, phase III trial; N= 790
Objective To determine whether docetaxel therapy at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in longer overall survival than that with ADT alone
Study Groups ADT plus docetaxel group (n= 397) and ADT-alone group (n= 393)
Methods Patients were randomly assigned to ADT alone or to combination therapy with ADT plus docetaxel at a dose of 75 mg per square meter of body-surface area given every 3 weeks for six cycles, with premedication with 8 mg of oral dexamethasone at 12 hours, 3 hours, and 1 hour before docetaxel infusion.
Duration July 2006 to December 2012
Primary Outcome Measure Overall survival
Baseline Characteristics The median age was 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 85% of the patients were white, approximately 70% had an ECOG performance-status score of 0, approximately 65% had high-volume disease, and approximately 60% had a Gleason score of 8 or higher (on a scale from 2 to 10, with higher scores indicating a more aggressive form of prostate cancer and a worse prognosis). In both groups, 73% of the patients had received no prior local therapy for prostate cancer with curative (rather than palliative) intent.   Among patients who started ADT before randomization, the median time from the start of ADT to randomization was 1.2 months (range, 0 to 3.9) in the combination group and 1.3 months (range, 0 to 3.9) in the ADT-alone group.
Results Median overall survival was 13.6 months longer in the ADT plus docetaxel group versus the ADT-alone group (57.6 months versus 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval, 0.47 to 0.80; p< 0.001)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone.

Results of this study demonstrated a clinically significant median 13-month survival increase in patients with hormone-sensitive metastatic prostate cancer receiving early administration docetaxel with ADT, specifically in patients with high-extent metastatic disease. While these findings suggest that many men with metastatic prostate cancer could benefit from receiving chemotherapy with androgen-deprivation therapy as first line treatment, patients should continue to be treated on a case-by-case basis, weighing out the potential risks versus benefits of treatment. Additionally, further follow-up from similar studies needs to be performed to help determine more precise benefits in patients with less extensive metastatic disease.

References

  1. Hormone (androgen deprivation) therapy for prostate cancer. American Cancer Society. Updated March 12, 2015. http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-hormone-therapy. Accessed August 24, 2015.
  2. Hormone Therapy for Prostate Cancer. National Cancer Institute. Reviewed June 23, 2014. http://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed August 24, 2015.
  3. Parker C, Gillessen S, Heidenreich A, Horwich A. Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015. doi: 10.1093/annonc/mdv222.
  4. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-46.
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