title: Tapentadol prolonged release for managing moderate to severe, chronic malignant tumor-related pain.
abstract: BACKGROUND
  Tapentadol prolonged release (PR) is effective and well tolerated for chronic osteoarthritis, low back, and diabetic peripheral neuropathic pain.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Randomized-withdrawal, parallel group, active- and placebo-controlled, double-blind phase 3 study (NCT00472303).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Hans G
authors: HG
authors: Kress
authors: E Dietlind
authors: ED
authors: Koch
authors: Hristiyan
authors: H
authors: Kosturski
authors: Achim
authors: A
authors: Steup
authors: Keith
authors: K
authors: Karcher
authors: Bernd
authors: B
authors: Lange
authors: Can
authors: C
authors: Dogan
authors: Mila S
authors: MS
authors: Etropolski
authors: Marëille
authors: M
authors: Eerdekens
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications*; D010636:Phenols / Q000627:therapeutic use*; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010636:Phenols; D009020:Morphine; D000077432:Tapentadol