Docetaxel rejected in first-line treatment of androgen-sensitive, metastatic prostate cancer


It has long been an open question whether early chemotherapy might benefit selected patients with androgen-sensitive prostate cancer. However, many trials seeking to answer this question have been unable to enroll sufficient patients to provide meaningful answers to this question.

We now have the final, published report of the results of the so-called GETUG-AFU 15 trial, which was a randomized, open-label, Phase III study that enrolled patients with metastatic, non-castrate (i.e., androgen-sensitive) prostate cancer at 29 centers in France and one in Belgium between October 18, 2004, and December 31, 2008. The investigators believed that early chemotherapy might improve the overall outcomes of patients with this type of prostate cancer, so they wanted to look at the effects of adding of docetaxel to androgen-deprivation therapy (ADT) for such patients.

Eligible patients had to be > 18 years of age; have histologically confirmed, metastatic adenocarcinoma of the prostate; have a life expectancy of ≥ 3 months; and have adequate hepatic, hematologic, and renal function. The patients were randomized to one or other of two regimens, as follows:

  • Regimen A: Androgen deprimation therapy (ADT) alone, through the use of orchiectomy or LHRH agonist therapy or LHRH therapy combined with a non-steroidal antiandrogen (such as flutamide or bicalutamide)
  • Regimen B: ADT in combination with docetaxel (75 mg/m2) given intravenously on the first day of each 21-day cycle for up to nine cycles.

The primary endpoint for the trial was overall survival. Greater detail about the trial structure can be found on the ClinicalTrials.gov web site.

Here are the key results of the study:

  • 193 patients were randomly allocated to receive treatment with Regimen A.
  • 192 patients were randomly assigned to receive treatment with Regimen B.
  • Average (median) follow-up was 50 months.
  • Average (median) overall survival was
    • 54.2 months for men treated on Regimen A
    • 58.9 months for men treated on Regimen B
  • No serious adverse events were reported in men treated on Regimen A.
  • 72 serious adverse events were reported in men treated on regimen B, including
    • 40 cases of neutropenia (in 21 percent of patients)
    • 6 cases of febrile neutropenia (in 3 percent of patients)
    • 3 cases of abnormal liver function (in 2 percent of patients)
    • 2 cases of neutropenia with infection (in 1 percent of patients).
  • Four treatment-related deaths occurred in among patients treated on Regimen B (of which two were neutropenia-related).

It should be noted that after the occurrence of these four treatment-related deaths, the data monitoring committee recommended treatment with granulocyte colony-stimulating factor among patients being treated with Regimen B, and no further treatment-related deaths occurred in this group of patients thereafter.

The authors conclude, bluntly, that,

Docetaxel should not be used as part of first-line treatment for patients with non-castrate, metastatic prostate cancer.

What this study does not, of course, tell us is whether very early chemotherapy may be a wise strategic choice for younger men with high-risk, localized or locally advanced prostate cancer. It has never been possible to enroll a sufficient number of patients into trials to test this hypothesis. We can undoubtedly expect some physicians to continue to try this early chemotherapy strategy is younger men with high-risk disease who ought to be able to deal well with the side effects of chemotherapy, but it would still be nice to know if this strategy was really effective (and sufficiently safe).

2 Responses

  1. I was diagnosed with advanced prostate cancer over 7 years ago. Never been treated with any form of chemotherapy, just hormone treatment and now in conjunction with abiraterone. PSA is 0.2; bone scans have always shown improvement, never worse. Anyone out there with this type of outcome?

  2. I am 49 years old and undergoig this treatment. I am receiving my third dose today. Hope this early treatment has a long-term positive effect. So far the treatments are rough but I am still able to work. I Will post more as the treatments continue. I hope I have good things to post.

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