Efficacy variables in patients with cancer versus patients without cancer treated with methylnaltrexone or placebo: An analysis of two placebo-controlled studies.

Abstract

1 Background: A post-hoc analysis of pooled data from two randomized, double-blind studies and their open-label extensions evaluated whether baseline characteristics and efficacy endpoints differ between cancer and noncancer adults with advanced illness and opioid-induced constipation treated with methylnaltrexone (MNTX) or placebo. Methods: Patients received SC MNTX 0.15 mg/kg or placebo (study 302) and SC MNTX 8 mg (38≤62 kg), 12 mg (≥62 kg), or placebo (study 4,000) every other day for two weeks and received the same doses of MNTX as needed during the first 2 weeks of the open-label extensions. Double-blind populations were stratified by those with/without cancer. Efficacy endpoints included rescue-free bowel movements (RFBMs) within 4 hours after each dose for ≥2 of the first 4 doses; time to rescue-free laxation; rescue laxatives use; and ≥3 RFBMs/week and ≥1 RFBM/week in ≥3 of 4 weeks. Results: Median baseline opioid use (mg/day) was greater in cancer (187.9 placebo [n=114]; 180.0 MNTX [n=116]) versus noncancer patients (80.0 placebo [n=71]; 120.0 MNTX [n=62]). MNTX significantly ( P<0.0001) improved the proportion of cancer (56.9%) and noncancer (58.1%) patients with an RFBM within 4 hours after each dose for ≥ two of the first four doses versus placebo (5.3% cancer; 11.3% noncancer). Median time to laxation was significantly ( P≤0.0002) shorter in cancer (0.96 hours) and noncancer (1.25 hours) patients 24 hours after the first dose of MNTX versus placebo (22.53 and >24 hours, respectively). Rescue laxatives were used by 39.7% of cancer and 30.6% of noncancer MNTX patients versus 51.8% of cancer and 39.4% of noncancer placebo patients. Of 108 open-label extension double-blind MNTX patients, 79 (73.1%) achieved ≥3 RFBMs/week with ≥1 RFBM/week increase in ≥ three of four weeks versus 48 (46.6%) of 103 double-blind placebo patients (data from double-blind and first two weeks of open-label). Conclusions: MNTX treatment improved the laxation response, with a faster onset of laxation in patients with and without cancer, and reduced the need for rescue laxatives vs placebo. Improvements over placebo continued into the first two weeks of the open-label extensions for MNTX-treated patients. Clinical trial information: NCT00672477, NCT00402038.