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Randomized Phase Ii Trial Of Weekly Docetaxel, Estramustine And Prednisone Versus Docetaxel And Prednisone In Patient With Hormone-Resistant Prostate Cancer

Phase 2
18 Years
Not Enrolling
Hormone Resistant Prostate Cancer, Metastatic Prostate Cancer

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Trial Information

Randomized Phase Ii Trial Of Weekly Docetaxel, Estramustine And Prednisone Versus Docetaxel And Prednisone In Patient With Hormone-Resistant Prostate Cancer

The addition of estramustine to other chemotherapeutic agents that affect microtubule
function may improve their efficacy15, 16, 17, 18. A phase III trial compared vinblastine
versus the combination of vinblastine plus estramustine as treatment for patients with
hormone-refractory prostate cancer. They showed that the association of estramustine and
vinblastine was superior to vinblastine alone for time to progression, PSA response and
survival (Hudes et al., ASCO 2002). In addition, Berry et al. found that
estramustine/paclitaxel improved PSA response rate but not overall survival compared with
paclitaxel alone (Berry et al. ASCO2001).

Similar association has been studied with docetaxel. In a phase I trial combining docetaxel
and estramustine19, 53% of patients reported a decrease in narcotic use and 63% experienced
a PSA response. In another phase I trial, a reduction in PSA of 50% or more was observed in
14 of 17 patients (82%)20. In a phase II trial involving 35 patients, a PSA response was
reported in 74% of the patients and objective response in 4 out of 7 patients with
measurable disease21. Median survival 22 months in this last study. These studies as well as
other support the combination of estramustine and docetaxel in the treatment of HRPC22, 23.

Recently, Oudard et al. competed a phase II randomized study comparing
mitoxantrone/prednisone versus docetaxel/estramustine prednisone24. Docetaxel was given
either weekly or every 3 weeks. Association of docetaxel/estramustine was found superior to
mitoxantrone in term of PSA response, (67-63% versus 18%), clinical benefit (79-56% versus
41%) and survival (19.2 months versus 11.6 months). In addition, toxicities of these
regimens were manageable and predictable. In this study, patients received 2 mgr of coumadin
to prevent thromboembolic event due to estramustine and only 7 % of the patients had
thrombosis. Other grade III & IV toxicities of the estramustine/docetaxel combination
included neutropenia (37% in the 3-week regimen and 0 % in the weekly regimen)
nausea/vomiting (2% in the 3-week regimen and 0 % in the weekly regimen), diarrhea (7% in
the 3-week regimen and 0 % in the weekly regimen). No febrile neutropenia was observed.

Although these data support a role for chemotherapy combinations, such as estramustine and
docetaxel, in the treatment of HRPC, further studies are needed to determine the relative
contribution of estramustine to the efficacy of docetaxel/estramustine regimen. In this
context, we propose to randomize patients with hormone resistant prostate cancer between
docetaxel/estramustine/prednisone and docetaxel/prednisone in a phase II study. The
principal endpoint will be the efficacy in term of PSA response. We chose to use the weekly
regimen as described by Oudard since the toxicity of this regimen is well described and is
easily manageable in our experience.

Inclusion Criteria:

- Signed informed consent prior to beginning protocol specific procedures.

- 18 years

- Histologically/cytologically proven prostate adenocarcinoma.

- Documented metastatic prostate adenocarcinoma

- Patients must have received prior hormonal therapy as defined below:

- Castration by orchiectomy and/or LHRH agonists with or without

- Antiandrogens

- Other hormonal agents (e.g., ketoconazole, ...)

- Testosterone level should be < 50 ng/dl in all patients (castrated level).

- Respect of antiandrogen withdrawal period

- No prior chemotherapy regimen at the exception of estramustine phosphate.

- documented disease progression defined either (i) by PSA increase and/or (ii)

- Prior radiation therapy (to less or equal than 25% of the bone marrow only) is
allowed. At least 4 weeks must have elapsed since the completion of radiation therapy
and the patient must have recovered from side effects.

- Prior surgery is allowed. At least 4 weeks must have elapsed since the completion of

- Life expectancy > 3 months.

- ECOG performance status 0-2.

- Normal cardiac function.

Exclusion Criteria:

- Prior chemotherapy except estramustine phosphate.(2)

- Prior isotope therapy

- Prior radiotherapy to >25% of bone marrow

- Prior malignancy except the following: adequately treated basal cell or squamous cell
skin cancer, or any other cancer from which the patient has been disease-free for >5

- Known brain or leptomeningeal involvement.

- Symptomatic peripheral neuropathy > grade 2

- Other serious illness or medical condition

- Concurrent treatment with other experimental drugs.

- Treatment with any other anti-cancer therapy (except LHRH agonists)

- Treatment with systemic corticosteroids used for reasons other than specified by the
protocol must be stopped prior to the administration of docetaxel.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To compare the efficacy of the association of Docetaxel and Estramustineand Prednisone versus Docetaxel and Prednisone in the treatment of hormone refractory prostate cancer in terms o PSA response

Outcome Time Frame:

within 30 days after end of treatment

Principal Investigator

Jean-Pascal Machiels, MD PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cliniques Universitaires St Luc


Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Study ID:

UCL-ONCO 04-001



Start Date:

December 2003

Completion Date:

February 2006

Related Keywords:

  • Hormone Resistant Prostate Cancer
  • Metastatic Prostate Cancer
  • prostate cancer
  • hormone resistant
  • metastatic
  • estramustine combine to docetaxel
  • randomized study
  • Prostatic Neoplasms