atients had experienced at least two relapses with sequelae or neurological deterioration within the previous 12 months. The average deterioration in EDSS was 2.2 points during the previous 12 months. During the screening period, patients were treated with two monthly doses of 1 g of IV MP and underwent monthly MRI scans. Only patients who developed at least one new Gd-enhancing MRI lesion during the 2-month screening period were eligible for randomization. A total of 42 eva luable patients received monthly treatments of 1 g of IV MP alone (n = 21) or ~12 mg/m2 of IV NOVANTRONE plus 1 g of IV MP (n = 21) (NOV + MP) for 6 months. Patients were eva luated monthly, and study outcome was determined after 6 months. The primary measure of effectiveness in this study was a comparison of the proportion of patients in each treatment group who developed no new Gd-enhancing MRI lesions at 6 months; these MRIs were assessed by a blinded panel. Additional outcomes were measured, including EDSS and number of relapses, but all clinical measures in this trial were assessed by an unblinded treating physician. Five patients, all in the MP alone arm, failed to complete the study due to lack of efficacy.
The results of this trial are displayed in Table 2.
Table 2 Efficacy Results Study 2
|
Primary Endpoint |
MP alone
(N = 21) |
NOV + MP
(N = 21) |
p-value |
|
MP = methylprednisolone; NOV + MP = NOVANTRONE plus methylprednisolone. |
|
* Results at Month 6, not including data for 5 withdrawals in the MP alone group. |
Patients (%) without new Gd-enhancing lesions on
MRIs (primary endpoint)* |
5 (31%) |
19 (90%) |
0.001 |
|
Secondary Endpoints |
|
|
|
|
EDSS change (Month 6 minus baseline)* (mean) |
-0.1 |
-1.1 |
0.013 |
|
Annualized relapse rate (mean per patient) |
3.0 |
0.7 |
0.003 |
|
Patients (%) without relapses |
7 (33%) |
14 (67%) |
0.031 |
Advanced Hormone-Refractory Prostate Cancer
A multicenter Phase 2 trial of NOVANTRONE and low-dose prednisone (N + P) was conducted in 27 symptomatic patients with hormone-refractory prostate cancer. Using NPCP (National Prostate Cancer Project) criteria for disease response, there was one partial responder and 12 patients with stable disease. However, nine patients or 33% achieved a palliative response defined on the basis of reduction in analgesic use or pain intensity.
These findings led to the initiation of a randomized multicenter trial (CCI-NOV22) comparing the effectiveness of (N + P) to low-dose prednisone alone (P). Eligible patients were required to have metastatic or locally advanced disease that had progressed on standard hormonal therapy, a castrate serum testosterone level, and at least mild pain at study entry. NOVANTRONE was administered at a dose of 12 mg/m2 by short IV infusion every 3 weeks. Prednisone was administered orally at a dose of 5 mg twice a day. Patients randomized to the prednisone arm were crossed over to the N + P arm if they progressed or if they were not improved after a minimum of 6 weeks of therapy with prednisone al |
