title: Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.
abstract: OBJECTIVE
  To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial.
  
  
  METHODS
  We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module.
  
  
  RESULTS
  Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level.
  
  
  CONCLUSIONS
  Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.
authors.affiliation: Department of Medicine, Princess Margaret Hospital, Toronto, Canada. ian-tannock@pmh.toronto.on.ca
authors.forename: I F
authors.initials: IF
authors.lastname: Tannock
authors.forename: D
authors.initials: D
authors.lastname: Osoba
authors.forename: M R
authors.initials: MR
authors.lastname: Stockler
authors.forename: D S
authors.initials: DS
authors.lastname: Ernst
authors.forename: A J
authors.initials: AJ
authors.lastname: Neville
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.forename: G R
authors.initials: GR
authors.lastname: Armitage
authors.forename: J J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: P M
authors.initials: PM
authors.lastname: Venner
authors.forename: C M
authors.initials: CM
authors.lastname: Coppin
authors.forename: K C
authors.initials: KC
authors.lastname: Murphy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use; D000726:Androgen Antagonists / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009919:Orchiectomy; D010146:Pain / Q000209:etiology; D010166:Palliative Care; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011788:Quality of Life; D015996:Survival Rate
chemical_list: D000700:Analgesics; D000726:Androgen Antagonists; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D011241:Prednisone