Randomized Placebo-Controlled Trial of Mitoxantrone/Prednisone and Clodronate Versus Mitoxantrone/Prednisone Alone in Patients With Hormone Refractory Metastatic Prostate Cancer and Pain
OBJECTIVES: I. Compare the effect of mitoxantrone and prednisone with or without clodronate
on localized bone pain in patients with hormone refractory metastatic prostate cancer. II.
Compare the overall survival and quality of life of these patients after these treatments.
OUTLINE: This is a randomized, double blinded, placebo controlled, multicenter study.
Patients are stratified according to quality of pain (mild vs moderate) and previous
corticosteroids or one regimen of non-anthracycline-containing cytotoxic chemotherapy (e.g.,
estramustine) vs none. Patients are assigned to 1 of 2 treatment arms. Arm I consists of
oral prednisone twice a day and intravenous mitoxantrone followed by intravenous clodronate
administered over 3 hours every 3 weeks. Arm II consists of oral prednisone twice a day and
intravenous mitoxantrone followed by intravenous placebo administered over 3 hours every 3
weeks. Doses are adjusted for myelosuppression. Treatment continues until disease
progression (although patients initially on placebo can continue on open-label clodronate)
or until the maximum cumulative dose of mitoxantrone is reached. Patients with a palliative
response may continue on prednisone and the study drug (clodronate or placebo) until disease
progression. Quality of life is assessed before and every 3 weeks during study treatment. A
daily pain diary is also maintained. All patients are followed at 2 weeks and then every 3
months until death.
PROJECTED ACCRUAL: This study will accrue 204 patients.
Allocation: Randomized, Primary Purpose: Treatment
Donald S. Ernst, MD, FRCPC
Tom Baker Cancer Centre - Calgary
United States: Federal Government