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Treatment of Prostate Cancer by Induction of Alternate Cell Death Pathways: A Phase I Trial of Docetaxel, Estramustine, Mitoxantrone and Prednisone

Phase 1
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

Treatment of Prostate Cancer by Induction of Alternate Cell Death Pathways: A Phase I Trial of Docetaxel, Estramustine, Mitoxantrone and Prednisone


- Determine the maximum tolerated doses of docetaxel and mitoxantrone in combination with
a fixed dose of estramustine and prednisone, when given to patients with advanced
prostate cancer.

- Characterize the toxicity of this treatment regimen in these patients.

OUTLINE: This is a dose escalation study of mitoxantrone and docetaxel. Patients are
stratified into one of two risk groups (good risk group or poor risk group) based on the
number of prior chemotherapy regimen(s) and the occurrence and sites(s) of prior radiation.

All patients receive oral prednisone twice daily on days 0-3, oral estramustine three times
daily on days 1-5, mitoxantrone IV bolus on day 2, and docetaxel IV over 1 hour on day 2.
Courses repeat every 21 days in the absence of unacceptable toxicity and disease
progression. Patients with stable disease may go off treatment after 6 courses.

Dose escalation proceeds independently for each risk group. Cohorts of 3 patients are
entered into each risk group. If 1 of 3 patients at a dose level experiences dose limiting
toxicity (DLT), then 3 additional patients are accrued into this level. If 2 of 6 patients
at a dose level experience DLT, then dose escalation stops and the maximum tolerated dose
(MTD) is defined at the previous dose level. At least 6 patients must be treated at the MTD.

Patients are followed every 3 months until death.

PROJECTED ACCRUAL: At least 12 patients (6 in each risk group) will be accrued into this

Inclusion Criteria


- Histologically confirmed adenocarcinoma of the prostate

- Failure of complete androgen ablation (orchiectomy or LHRH and antiandrogen therapy)
as manifested by at least 1 of the following criteria:

- Rise in serum PSA greater than 50% of nadir confirmed on 2 measurements 1 week

- Appearance of new lesions on bone scan

- Appearance of new soft-tissue lesions

- Measurable or evaluable disease

- No brain or leptomeningeal involvement



- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Greater than 3 months


- WBC at least 3,500/mm3

- Absolute neutrophil count at least 1,500/mm3

- Platelet count at least 100,000/mm3


- Bilirubin no greater than upper limit of normal (ULN)

- Alkaline phosphatase no greater than 5 times ULN

- SGOT and SGPT no greater than 2 times ULN


- Creatinine no greater than 2 times ULN


- No history of coagulopathy

- No myocardial infarction in the last 6 months

- No history of cardiovascular accident

- No history of congestive heart failure


- No symptomatic peripheral neuropathy greater than grade 1

- No history of significant neurologic or psychiatric disorders including psychotic
disorders, dementia, or seizures


- No history of pulmonary embolus


- Testosterone no greater than 3.5 nmol/L

- No contraindications to glucocorticoid therapy such as uncontrolled diabetes mellitus
or active peptic ulcer disease

- No active infection

- No other serious illness or medical condition

- No other concurrent or prior malignancy in the past 5 years except previously excised
or curatively irradiated nonmelanoma skin cancer


Biologic therapy:

- Not specified


- At least 4 weeks since prior chemotherapy

Endocrine therapy:

- See Disease Characteristics

- At least 4 weeks since prior hormonal therapy (including nonsteroidal antiandrogens,
but not LHRH agonists)


- No prior radiotherapy to greater than 30% of bone marrow

- At least 6 weeks since isotope therapy

- At least 4 weeks since prior radiotherapy


- See Disease Characteristics


- At least 4 weeks since prior investigational drugs

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Daniel P. Petrylak, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Herbert Irving Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

August 1998

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage IV prostate cancer
  • recurrent prostate cancer
  • Prostatic Neoplasms



Herbert Irving Comprehensive Cancer Center at Columbia University New York, New York  10032