Silvestri, B., Bandieri, E., Del Prete, S., Ianniello, G.P., Micheletto, G., Dambrosio, M., . . . Spanu, P. (2008). Oxycodone controlled-release as first-choice therapy for moderate-to-severe cancer pain in Italian patients: Results of an open-label, multicentre, observational study. Clinical Drug Investigation, 28(7), 399–407.

To evaluate the safety and efficacy of conrolled-release (CR) oxycodone as first-line opioid treatment for moderate to severe cancer-related pain

Every 12 hours for 21 days, patients were treated with oxycodone CR monotherapy. Initial doses were individualized for each patient. Doses were up-titrated for 3–4 days until the treatment achieved effective pain control. Effective pain control was a pain-rating reduction of 30% or more, compared to the previous pain rating value, and by day 7 a reduction in pain value equal to or less than 3. Hospital- based medical practitioners collected data at baseline and on days 1, 3, 7, 14, and 21.

• The sample was composed of 334 patients.
• Mean patient age was 66 years (SD = 11 years). 
• Of all patients, 44.6% were female and 55.4% were male.
• The sample included a variety of cancer types, with the most frequent diagnoses being lung, breast, prostate, and colon cancer (37.9% of these cases included bone metastases).
• Of all patients, at study entry 62.8% had experienced cancer-related pain for three months or less. At study entry, all patients had a pain intensity rating equal to or greater than 4 and 72% had baseline pain equal to or greater than 7. Of all patients, 68.2% had been using NSAIDs or weak opioids for the relief of pain.

• Multisite
• Italy

Open-label observational trial

• Numeric rating scale (0–10), to measure pain
• Short-Form Health Survey, 36 items (SF-36)
• Data related to adverse events, as recorded by clinicians

Pain intensity decreased consistently throughout the 21-day trial period, and the study drug achieved a significant decrease in pain intensity after just one day of treatment (p = 0.00001). Clinicians had to increase the dose over the course of the study, beginning with a mean dose of 22.84 mg/day on day 1 to a mean of 40 mg/day by day 21. Four patients discontinued treatment because of uncontrolled pain, which may have been the result of lack of dose escalation. Treatment with oxycodone CR improved quality-of-life parameters by 48%–63%, with the greatest improvement being in sleep quality and concentration. Drug-related adverse events were reported in 4% of patients and were of mild to moderate intensity. Nausea, vomiting, and constipation were the most common drug-related adverse events.

Oxycodone CR, provided as first-line treatment for moderate to severe cancer pain, was safe and effective.

• The study had a risk of bias due to no appropriate control group.
• Authors did not discuss the presence, absence, or treatment of breakthrough pain.

The World Health Organization and European Association of Palliative Care, among others, recommend that immediate-release formulations of strong opioids be titrated. This recommendation is based on consensus expert opinion rather than evidence from clinical trials. This study demonstrates that controlled-release formulations can be titrated. The results may be rapid response and significant reduction in pain intensity. In addition, in this study pain relief provided by oxycodone CR was associated with improved sleep quality.