gators at Cancer and Leukemia Group B (CALGB) conducted a Phase 3 comparative trial of NOVANTRONE plus hydrocortisone (N + H) versus hydrocortisone alone (H) in patients with hormone-refractory prostate cancer (CALGB 9182). Eligible patients were required to have metastatic disease that had progressed despite at least one hormonal therapy. Progression at study entry was defined on the basis of progressive symptoms, increases in measurable or osseous disease, or rising PSA levels. NOVANTRONE was administered intravenously at a dose of 14 mg/m2 every 21 days and hydrocortisone was administered orally at a daily dose of 40 mg. A total of 242 subjects were randomized, 119 to the N + H arm and 123 to the H arm. There were no differences in survival between the two arms, with a median of 11.1 months in the N + H arm and 12 months in the H arm (p = 0.3298).
Using NPCP criteria for response, partial responses were achieved in 10 patients (8.4%) randomized to the N + H arm compared with 2 patients (1.6%) randomized to the H arm (p = 0.018). The median time to progression, defined by NPCP criteria, for patients randomized to the N + H arm was 7.3 months compared to 4.1 months for patients randomized to H alone (p = 0.0654).
Approximately 60% of patients on each arm required analgesics at baseline. Analgesic use was measured in this study using a 5-point scale. The best percent change from baseline in mean analgesic use was -17% for 61 patients with available data on the N + H arm, compared with +17% for 61 patients on H alone (p = 0.014). A time trend analysis for analgesic use in individual patients also showed a trend favoring the N + H arm over H alone but was not statistically significant.
Pain intensity was measured using the Symptom Distress Scale (SDS) Pain Item 2 (a 5-point scale). The best percent change from baseline in mean pain intensity was -14% for 37 patients with available data on the N + H arm, compared with +8% for 38 patients on H alone (p = 0.057). A time trend analysis for pain intensity in individual patients showed no difference between treatment arms.
Acute Nonlymphocytic Leukemia
In two large randomized multicenter trials, remission induction therapy for acute nonlymphocytic leukemia (ANLL) with NOVANTRONE 12 mg/m2 daily for 3 days as a 10-minute intravenous infusion and cytarabine 100 mg/m2 for 7 days given as a continuous 24-hour infusion was compared with daunorubicin 45 mg/m2 daily by intravenous infusion for 3 days plus the same dose and schedule of cytarabine used with NOVANTRONE. Patients who had an incomplete antileukemic response received a second induction course in which NOVANTRONE or daunorubicin was administered for 2 days and cytarabine for 5 days using the same daily dosage schedule. Response rates and median survival information for both the U.S. and international multicenter trials are given in Table 3:
Table 3 Response Rates, Time to Response, and Survival in U.S. and International Trials
|
Trial |
% Complete
Response (CR) |
Median Time
to CR (days) |
Survival (days) |
|
NOV = NOVANTRONE® + cytarabine |
|
DAUN = daunorubicin + cytarabine |
|
|
NOV |
DAUN |
NOV |
DAUN |
NOV |
DAUN |
|
U.S. |
63 (62/98) |
53 (54/102) |
|
|
