Sima, L., Fang, W.X., Wu, X.M., & Li, F. (2012). Efficacy of oxycodone/paracetamol for patients with bone-cancer pain: A multicenter, randomized, double-blinded, placebo-controlled trial. Journal of Clinical Pharmacy and Therapeutics, 37, 27–31.

To determine whether patients with bone cancer pain who were already administered opioids obtain clinically important pain control with regular oxycodone/paracetamol

Patients received one to three placebo or oxycodone/paracetamol tablets four times per day for days 1–3, with the dosage titrated step by step based on pain assessment, up to 12 tablets per day, maximum. Patients recorded pain diary entries at baseline and on the study days. Immediate-release oral morphine was used to control breakthrough pain with 10% dose increments of the background continuous-release opioid, with no maximum (these were dispensed to the patient at the beginning of the study with specific instructions on administration). Patients remained on current background analgesic management, and additional analgesic drugs could be used, but not altered, during the study period.

• A total of 246 patients began the trial, with 225 completing the three-day study.    
• Patient age range was 28–84 years.
• Of the sample, 122 were male and 124 were female.
• Patients had malignant solid tumors with bone metastasis confirmed via imaging, had bone-related pain rated as 4 or higher on an 11-point pain scale, and had received treatment with controlled-release morphine or transdermal fentanyl patches for one week or more. They had conscious mental status, the ability to take oral tablets, and were at least 18 years of age.
• Patients were excluded from the study if they had received chemotherapy, radiation, or endocrine or monoamine oxidase inhibitors within the previous 30 days (or during the study), had history of alcohol abuse or severe hepatic disease, or had received nonsteroidal anti-inflammatory drugs or paracetamol combinations.

• Multisite
• Home setting
• Beijing, China

The study has clinical applicability for late effects and survivorship, and end-of-life and palliative care.

The study was a multicenter, randomized, double-blinded, placebo-controlled trial.

• Pain Intensity Difference
• Short Form-6 Dimensions quality-of-life scale
• General impression of patient satisfaction with the treatment (five-point verbal rating scale, 0 = poor, 4 = excellent)
• Numerical rating score (11-point scale, 0 = no pain, 10 = worst pain imaginable)
• Qualitative data analyzed using chi-squared test
• Qualitative data analyzed using Fisher’s exact test

Prior to the study, 55.6% of the intervention group experienced breakthrough pain, while 50.8% of the placebo group did. After treatment, only 38% of the intervention group suffered breakthrough pain, while 58% of the placebo group did. The use of immediate-release morphine decreased from 50% to 27.8% in the intervention group while in the study, whereas the placebo group decreased from 46.7% pre to 43.3% in the same time frames.

When oxycodone/paracetamol is added to intermediate- or high-dose continuous-release opioids, patients with bone cancer pain experienced greater relief of pain.

The authors cite that the study was conducted on only Chinese patients and point to the need to consider other ethnicities. There is no analysis based on overall analgesic regimens used, and no full description of these.  Addition of this medication essentially increased the opioid dosing per day, so it is not clear whether this particular formulation was any more helpful than simple dosage increases.

This study is applicable to patients with bone cancer pain who experience significant breakthrough pain while taking relatively high doses of a continuous-release opioid. It is not clear from this study how this particular formulation fits into an overall pain management regimen because it did provide higher dosage of opioid. Increasing opioid dosages may have had the same effect.