Leppert, W., & Majkowicz, M. (2010). The impact of tramadol and dihydrocodeine treatment on quality of life of patients with cancer pain. International Journal of Clinical Practice, 64(12), 1681–1687.

To compare the impact of tramadol to that of dihydrocodone (DHC) treatment on the quality of life (QoL) and performance status (PS) of patients with cancer pain  

Patients received treatment with either tramadol or DHC controlled-release tablets for seven days. Then drugs were switched and administered for another seven days. QoL and PS were measured at baseline, at the 7th day, and on the 14th day of therapy.

• The sample was composed of 30 patients who completed the study; 40 patients were recruited for the study.
• Mean patient age was 70.5 years.
• Of all patients in the sample, 37% were female and 63% were male.
• The majority of patients had had these cancer diagnoses: lung cancer (four patients), colon cancer (four patients), stomach cancer (three patients), and tonsil cancer (two patients).
• Patients were included if they
  • Had received a cancer diagnosis.
  • Were over the age of 18 years.
  • Were opioid-naive.
  • Had no history of drug abuse.
  • Were capable of taking the medications by mouth.
  • Could communicate normally and fill out questionnaires.
  • Were experiencing nociceptive baseline pain intensity of more than 40 on 0–100 scale during nonopioid therapy.
  • Had no renal impairment.
  • Were not pregnant or lactating.

• Single site
• Inpatient
• One inpatient palliative medicine unit
   

• Phase of care: end-of-life care
• Clinical applications: end-of-life and palliative care, late effects and survivorship

Randomized crossover trial

• Visual analog scale, or VAS (0 = no pain, 100 = the worst possible pain), to measure pain intensity at baseline (before administration of analgesics) and during tramadol and DHC treatment (days 1–14)
• European Organization for Results and Treatment of Cancer quality of life questionnaire (EORTC QLQ C-30), an instrument developed for use in international clinical trials in oncology, which includes scales measuring physical, role (work), cognitive, emotional, and social functioning and global QoL as well as symptom-measuring scales relating to fatigue, nausea and vomiting, pain, dyspnea, sleep, appetite, constipation, diarrhea, and finances.   
• Eastern Cooperative Oncology Group (ECOG) scale and Karnofsky Performance Status Score, to measure performance status. (Authors did not describe performance measurement in detail. Performance status is the dependent variable; the independent variables are drug influence, treatment time effect, and interaction of drug and treatment time.)
   

• More patients in the tramadol group (12 patients) used rescue analgesics than did patients in the DHC group (8).
• Nineteen patients preferred DHC treatment, and four patients favored tramadol therapy. Seven patients thought that both analgesics were equally effective.
• ANOVA for functional scales of EORTC QLQ-C30 showed higher scores of emotional functioning in the tramadol group and higher global QoL and better cognitive functioning in the DHC group. Authors noted a trend toward better physical functioning in the DHC group (p = 0.063 for treatment time, p = 0.09 for interaction of drug and treatment time).
• In the DHC group, regarding symptom scales pertaining to drug and treatment time interaction, results of two-way ANOVA showed less fatigue (p < 0.01), pain (p < 0.001), sleep disturbance (p < 0.005), and nausea and vomiting (p < 0.001) and better appetite (p < 0.039).

DHC treatment was associated with better global QoL, cognitive functioning, analgesia, and appetite and with less fatigue, sleep disturbances, nausea, and vomiting. Tramadol therapy was associated with better emotional functioning, less constipation, and fewer financial problems. Performance status deteriorated in both groups.

• The study had a small sample, with fewer than 100 patients.
• The study had a risk of bias due to no control group, no blinding, and no washout period before the drug switch.
• The treatment period for each analgesic (seven days for each) was very brief.

Findings suggest that the decision between tramadol and DHC should be based on each patient's status and symptoms of concern. To date, no other studies have compared tramadol to DHC in patients with cancer-elated pain. Further research would be beneficial.