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Randomized Trial of Epoetin Alfa in Men With Hormone-refractory Prostate Cancer and Anemia.

Phase 3
18 Years
Not Enrolling
Prostate, Carcinoma

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Trial Information

Randomized Trial of Epoetin Alfa in Men With Hormone-refractory Prostate Cancer and Anemia.

Anemia is a common problem experienced by patients with malignancy. Although cancer
treatment such as systemic chemotherapy is an obvious cause, many cancer patients are anemic
at presentation. Estimates in prostate cancer patients suggest that nearly 40% present with
hemoglobin levels less than 120 g/L. The most common clinical manifestation of anemia is
fatigue, although vertigo, loss of appetite, poor concentration and dyspnea (shortness of
breath) can also occur. Anemia often leads to impairment of physical capacity, lowers
patients' subjective sense of well-being, and diminishes their overall quality-of-life
(QoL). The use of recombinant erythropoietin for patients with chronic anemia of end stage
renal disease, acquired immune deficiency syndrome, or anemia of chronic disease in the
setting of malignancy (cancer) is well established to provide benefit in reducing
transfusion requirements. There exists a number of published data on QoL in cancer
patients. Abels et al. published in 1991 initial results of clinical reports that
specifically reported on QoL outcomes. The study actually consisted of a series of three
concurrent randomized, double blind, placebo controlled trials conducted on groups of
patients with a variety of underlying malignancies. The three studies included 124 patients
not previously treated with systemic therapy, 132 patients treated systemically with
cisplatinum containing chemotherapy regimens and 157 patients treated with non-cisplatinum
containing regimens respectively. All patients had pre-treatment hemoglobins of less than
105 g/L or hematocrits (percentage of red blood cells in blood) of less than 32%. In each
trial, patients randomized to receive recombinant erythropoietin had significantly greater
increases in hematocrit than placebo patients. QoL parameters (as measured on a visual
analog scale) were significantly improved in patients receiving erythropoietin who
demonstrated an increase in hematocrit throughout the three studies. Overall QoL improved
significantly over baseline, although individual studies only demonstrated a trend towards
improvement. Littlewood et al. published in 2001 the results of a double-blind, placebo
controlled multi-center study of 375 cancer patients receiving non-platinum containing
chemotherapy. A baseline hemoglobin of less than or equal to 105 g/L, or a drop of 20 g/L
with chemotherapy was required for eligibility. Patients were randomized 1:2 to either
placebo or epoetin alfa, for up to 4 weeks following chemotherapy. Active treatment
demonstrated significant effectiveness in increasing hemoglobin levels and reducing
transfusion requirements. Significant improvement in all primary cancer- and anemia-specific
QoL domains favoured epoetin alfa. Although clinical evidence suggests benefit beyond
reduced transfusion requirements, many studies looking at impact on QoL have been
uncontrolled by design, with variable quality and collection of QoL data. Since they have
also involved patients with a myriad of primary malignancies, and previous therapies, the
translation of results to site and situation specific clinical practice has been difficult.
As erythropoiesis is a complex process that depends on inhibiting or stimulating cytokines,
which may be regulated differently among various neoplastic diseases (i.e. different tumour
types), studies in more homogenous groups of patients were deemed necessary to evaluate
impact on QoL. Prostate cancer is the most common serious cancer in men. Despite advances in
screening and treatment, progression to the incurable metastatic phase of the disease
remains common. Androgen ablation therapy using surgery or drugs remains the standard of
treatment, but inevitably, androgen resistance develops. Hormone refractory prostate cancer
represents a spectrum of disease ranging from asymptomatic patients with only biochemical
evidence of androgen resistance to end-stage disease characterized by extensive bone
metastases, pain, wasting, reduced QoL, and a median survival of less than one year.
Treatment of hormone refractory prostate cancer does not prolong survival, but may improve
symptoms and QoL. Anemia is common in this group of patients, with hemoglobin levels of less
than 120 g/L often seen (in up to 40% patients). Patients are also genrally older, often
have co-morbid conditions, and transfusions for palliation are frequently given. A
randomized, placebo-controlled study evaluating an intervention with epoetin alfa that could
significantly improve QoL was thus carried out in hormone refractory prostate cancer
patients. It was deemed that such an intervention, if successful, could have the potential
to change current clinical practice. Moreover, improved QoL, in response to increased Hb
levels, could also lead to a reduction in hospital admissions and to fewer transfusions in
this patient population.

Patients were to receive either 40,000 IU epoetin alfa weekly or matching placebo
subcutaneously for 16 weeks.

Inclusion Criteria:

- Patients with histological confirmed adenocarcinoma of the prostate or patients who
have metastatic carcinoma of presumptive prostate origin as manifest by the presence
of sclerotic bony metastases and a serum PSA level greater than the upper limit of

- Hemoglobin level at or below 120 g/L

- ECOG (Eastern Cooperative Oncology Group) Performance status of 0-2.      

Exclusion Criteria:

- No known or suspected CNS metastasis (Cancer that has spread from the original
(primary) tumor to the central nervous system)

- No other active concurrent malignancy, other than the underlying prostate cancer
which is expected to influence QoL

- No blood transfusions within the last 14 days and no previous use of erythropoietin
(i.e., that would impact baseline Hb)

- No anemia due to factors other than cancer/radiotherapy (i.e., hemolysis or
gastrointestinal bleeding, evidence of untreated folate or vitamin B12 deficiency)

- No history of uncontrolled hypertension or diastolic blood pressure greater than 100

- No mental incompetence, including psychiatric or addictive disorders which would
preclude meaningful completion of quality-of-life questionnaires.      

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

The primary outcome was change in Quality of Life (FACT-An Anemia scale) from baseline to 16 weeks.

Principal Investigator

Janssen-Ortho Inc. Clinical Trial

Investigator Role:

Study Director

Investigator Affiliation:

Janssen-Ortho Inc., Canada


United States: Institutional Review Board

Study ID:




Start Date:

December 2002

Completion Date:

March 2006

Related Keywords:

  • Prostate
  • Carcinoma
  • Hormone refractory prostate cancer
  • Anemia
  • Quality-of-life
  • Carcinoma
  • Prostatic Neoplasms