Tapentadol Prolonged Release for Managing Moderate to Severe, Chronic Malignant TumorRelated Pain

Abstract

Background: Tapentadol prolonged release (PR) is effective and well tolerated for chronic osteoarthritis, low back, and diabetic peripheral neuropathic pain. Objectives: To evaluate the efficacy and tolerability of tapentadol PR compared with placebo and morphine controlled release (CR) for managing moderate to severe chronic malignant tumor-related pain. Study Design: Randomized-withdrawal, parallel group, active- and placebo-controlled, double-blind phase 3 study (NCT00472303). Setting: Primary, secondary, and tertiary care settings in 16 countries. Methods: Eligible patients (pain intensity ≥ 5 [11-point numerical rating scale] on prior analgesics) were randomized (2:1) and titrated to their optimal dose of tapentadol PR (100 – 250 mg bid) or morphine sulfate CR (40 – 100 mg bid) over 2 weeks. Morphine sulfate immediate release 10 mg was permitted as needed for rescue medication (no maximum dose). Patients who completed titration and, during the last 3 days of titration, had mean pain intensity < 5 (based on twice-daily ratings) and mean rescue medication use ≤ 20 mg/day continued into a 4-week maintenance period; patients who received morphine CR during titration continued taking morphine CR, and those who received tapentadol PR were re-randomized (1:1) to tapentadol PR or placebo bid. Response during maintenance (primary efficacy endpoint) was defined as having: 1) completed the maintenance period, 2) a mean pain intensity < 5 during maintenance, and 3) used an average of ≤ 20 mg/day of rescue medication during maintenance. Response at the end of titration was defined similarly, with pain intensity and rescue medication averages based on the last 3 days of titration. Results: Of 622 patients screened, 496 were randomized, treated during titration, and evaluable for safety; 327 were re-randomized, treated during maintenance, and evaluable for safety; and 325 were evaluable for efficacy. The adjusted responder rate estimate during maintenance (logistic regression adjusting for treatment group, pooled center, and pain intensity at start of maintenance) was significantly higher with tapentadol PR (64.3%) than with placebo (47.1%; odds ratio (OR), 2.02 [95% confidence interval (CI), 1.12 – 3.65]; P = 0.02). Based on responder rates at the end of titration, tapentadol PR (76.0% [174/229]) was non-inferior to morphine CR (83.0% [83/100]). The lower limit of the 95% CI for the between-groups difference (−15.5%) was within the pre-specified 20% non-inferiority margin. During titration, incidences of treatment-emergent adverse events (TEAEs) were 50.0% (169/338) with tapentadol PR and 63.9% (101/158) with morphine CR; incidences of nausea, vomiting, and dry mouth were lower with tapentadol PR than with morphine CR. During maintenance, incidences of TEAEs were 56.3% (63/112), 62.3% (66/106), and 62.4% (68/109) with placebo, tapentadol PR, and morphine CR, respectively. Limitations: Statistical comparisons between tapentadol PR and morphine CR were limited to descriptive statistics during the maintenance period because of the pre-selection of responders to tapentadol PR or morphine CR during titration. Conclusions: Results obtained during maintenance indicate that tapentadol PR (100 – 250 mg bid) is effective compared with placebo for managing moderate to severe chronic malignant tumor-related pain. Based on results obtained during titration, tapentadol PR provides comparable efficacy to that of morphine sulfate CR (40 – 100 mg bid), but is associated with better gastrointestinal tolerability. Key words: Tapentadol PR, cancer pain, tumor-related pain, malignant pain, chronic pain, morphine CR, non-inferiority, efficacy, tolerability

Assessment and manifestation of central sensitisation across different chronic pain conditions

“…The effect of repeated dosing with tapentadol matches very well many chronic pain conditions (Riemsma et al., ) with impaired CPM such as OA pain (Steigerwald et al., ), LBP (Buynak et al., ; Steigerwald et al., ; Baron et al., ), painful peripheral diabetic neuropathy (Schwartz et al., ; Vadivelu et al., ), and cancer pain (Kress et al., ).…”

Tapentadol in Cancer Patients with Neuropathic Pain: A Comparison of Methadone, Oxycodone, Fentanyl, and Hydromorphone

“…21) CYP2B6*6 is reported to reduce the expression and activity of CYP2B6 significantly 22) ; the incidence of CYP2B6*6 tends to be lower in Japanese than in Western patients. 23) Taking these reports into consideration, it is expected that the clearance of methadone in Japanese individuals will increase. However, in this study, the reduction in the VRS score and the average use of opioid rescue drugs on day 14 was significantly larger in the methadone group than in the oxycodone group.…”

Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients

“…According to a narrative review focusing on tapentadol for the palliation of cancer pain in adults [58], the research evidence from non-randomized, open-label or clinical practice studies suggests that tapentadol may be well tolerated when used in the ambulatory care setting, with few, typically mild adverse reactions, such as dizziness, loss of appetite, and nausea. To date, only three published randomized controlled trials have compared tapentadol to either placebo or an active control in patients with moderate to severe cancer pain, two of which were conducted in Japan and South Korea [59][60][61]. However, these studies were small and used heterogeneous designs, preventing the pooling of data for statistical analyses [58,62].…”