Primary Outcome Measures:
- Percentage of subjects with CR or PR [ Time Frame: evaluated after 2 courses then every other course ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Hematologic toxicity [ Time Frame: evaluated @ baseline & 3/wk during treatment or until recovery ] [ Designated as safety issue: Yes ]
- Percentage of subjects with >/= Grade 3 hematopoietic & non-hematopoietic toxicities [ Time Frame: labs evaluated @ baseline & 3/wk during treatment or until recovery; toxicity evaluated through treatment or until resolved ] [ Designated as safety issue: Yes ]
- Clinical non-hematologic & hematologic toxicity [ Time Frame: continuous throughout study ] [ Designated as safety issue: Yes ]
- QOL [ Time Frame: baseline then every other cycle ] [ Designated as safety issue: No ]
- Fraction delivered vs. intended Doxil [ Time Frame: each dose ] [ Designated as safety issue: No ]
- Cytokines [ Time Frame: evaluated days 1, 5, 8 every other cycle ] [ Designated as safety issue: Yes ]
- Survival [ Time Frame: evaluated through study ] [ Designated as safety issue: No ]
Primary Objectives:
To assess the anti-tumor activity of Doxil by assessing response rates in patients with hormone refractory prostate cancer with or without dexamethasone pre-treatment.
Secondary Objectives:
To assess and estimate in patients with hormone refractory prostate cancer treated with Doxil with or without pre-treatment dexamethasone: 1) overall survival 2) toxicity, 3) quality of life parameters, 4) dose intensity administered in both treatment groups.
Study Design:
We will perform an open labeled, parallel, randomized phase II study using a two-stage design to determine if there is sufficient anti-tumor activity in either arm to warrant further study. Assumptions made in this study: an unacceptable overall response rate is </= 10% and we will pursue further study if the overall response rate is >/= 30%. The overall response rate for this study will be based on the total number of responses observed defined as: complete responses + partial responses (both by RECIST)+biochemical responses (in patients with no measurable target lesions a >/= 50% decrease in PSA for >/= 4 weeks). Fifteen patients will be randomized in the first phase (to both Arm 1 and Arm 2). No further patients will be accrued if <2/15 responses are noted in a given arm. Ten additional patients will be enrolled if >/= 2/15 responses are observed. If there are >/= 5/25 responses then further studies will be pursued with that regimen. We will determine the overall incidence and severity of toxicities in both arms.
Treatment:
Arm 1: Doxil: Dose: 50 mg/m2, IV. Frequency: day 5 of each 28 day cycle. Arm 2: Doxil: Dose: 50 mg/m2, IV. Frequency: day 5 of each 28 day cycle. Arm 1 only: Dexamethasone: Dose: 12 mg bid po. Frequency: days 1,2,3,4,5 of each 28 day cycle.
Number of Cycles for both Arm 1 and 2: until progression or unacceptable toxicity develops.