Kress, H.G., Koch, E.D., Kosturski, H., Steup, A., Karcher, K., Lange, B., . . . Eerdekens, M. (2014). Tapentadol prolonged release for managing moderate to severe, chronic malignant tumor-related pain. Pain Physician, 17, 329–343.

To determine whether tapentadol prolonged-release (PR) is effective and tolerable for managing moderate to severe tumor-related pain

Patients whose pain was rated 5 or above on an 11-point scale were randomized (2:1) and titrated to an optimal dose of tapentadol PR (100–250 mg BID) or morphine sulfate CR (40–100 mg BID) over two weeks. Immediate-release morphine sulfate was allowed as needed as a breakthrough medication. During the last three days of titration, patients who achieved an average pain intensity of less than 5 and took less than 20 mg per day of rescue pain medication entered a four-week maintenance period. Patients who received tapentadol were rerandomized (1:1) to either tapentadol BID or a placebo for the maintenance period. Response at the end of titration and response at the end of the maintenance were assessed. Tolerability and side effects were evaluated.

• N = 327
• AGE = 68% < 65 years, 32% ≥ 65 years
• MALES: 53%, FEMALES: 47%
• KEY DISEASE CHARACTERISTICS: The most common neoplasms included were breast and nipple cancers and non-small cell neoplasms of the respiratory tract. Metastases were present in greater than 75% of all patients.   

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: 71 sites in 16 countries

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Randomized-withdrawal, parallel-group, active- and placebo-controlled, double-blinded study

During the study, pain levels were evaluated with an 11-point Numeric Rating Scale (NRS) twice daily. The proportion of patients classified as responders (patients who completed 28 or more days, had a mean pain intensity score < 5, and had a mean total daily dose of ≤ 20 mg rescue medication during the maintenance period) was evaluated as a primary endpoint during the titration and maintenance periods. Mean pain intensity at the start of the maintenance period was calculated as the mean daily pain intensity scores during the last three days of the titration period. Mean weekly pain intensity during the maintenance period was calculated from the mean daily pain intensity scores during each week of the maintenance period. Adverse events were coded using the Medical Dictionary for Regulatory Activities v15.0. The treatments for emergent adverse events in all groups were collected and compared as were specific gastrointestinal and nervous system effects and general disorders or administration site effects.

Patients receiving tapentadol were twice as likely to respond than the patients who received a placebo. Tapentadol PR was noninferior to morphine CR (p < 0.001). Mean pain intensity scores improved in both the tapentadol PR and morphine CR groups during titration. These reductions were sustained throughout the maintenance period. There were no statistically significant differences between the tapentadol and placebo groups in changes in pain intensity from the start of maintenance to weeks 1–4 (p ≥ 0.0152). A higher percentage of patients in the placebo group (72.1%) took ≥ 20 mg per day of rescue morphine immediate-release compared to the tapentadol (71.4%) or morphine CR (61.5%) groups. During titration, 50% of patients in the tapentadol group and 63.9% of patients in the morphine group reported one or more treatment-emergent adverse effects (TEAEs). A smaller percentage of patients receiving tapentadol PR had any TEAEs (p = 0.0039) than those receiving morphine CR.

Tapentadol PR 100–250 mg BID was effective in the treating tumor-related pain. The analgesic effect of tapentadol PR was not inferior to morphine CR and had better overall and gastrointestinal tolerability than morphine CR. However, more tapentadol users required rescue pain medication than those taking morphine CR.

• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: The comparison of tapentadol PR and morphine CR was limited to two weeks because of the study design.

Tapentadol, one of a new class of centrally acting analgesics, was effective in treating tumor pain and was generally better tolerated than morphine CR. Nurses should be familiar with the common side effects associated with this medication including nausea, vomiting, constipation, dizziness, sleepiness, and fatigue to safely care for patients receiving this drug.