High dosage of a fixed combination oxycodone/naloxone prolonged release: efficacy and tolerability in patients with chronic cancer pain.

PURPOSE: Opioids are associated with side effects in the treatment of moderate-to-severe chronic cancer pain. Oral combination of opioid agonist-antagonist oxycodone-naloxone (OXN-PR) attenuates gastrointestinal side effects; however, evidence on high-dose OXN-PR treatment is scant. This study evaluates the efficacy and tolerability of high-dose OXN-PR in chronic cancer pain.

PATIENTS AND METHODS: This was a multicenter, prospective 60-day observation on consecutive cancer patients with uncontrolled moderate-severe chronic pain or intolerant to other analgesics, who were switched at entry visit (T0) to OXN-PR ≥80 mg daily. Patients were reassessed 14, 30, 45, and 60 days later (T60). Primary endpoint of the study was analgesic response rate (decrease ≥30% of pain intensity from baseline, measured on a 0-10 numerical rating scale, NRS) after 30 days on OXN-PR. Additional endpoints assessed at every visit were the impact of pain on quality of life (QoL), breakthrough cancer pain (BTCP) episodes, opioid dosage escalation index, bowel dysfunction, safety, and other side effects.

RESULTS: One hundred nineteen patients were included (age 64 ± 12, metastatic disease in 91.6%); 101 of them (84.9%) completed the 60-day observation. At T0, the majority had severe pain (NRS ≥7 in 79.8%; neuropathic features in 83.2%). Response rate at 30-day visit was 79.8% (n = 95). OXN-PR resulted in a significant reduction in pain over time (T0: 7.4 ± 1.3; T60: 3.3 ± 1.8; p < 0.001), and the number of daily (BTCP) declined (3.9 ± 2.2 vs. 2.0 ± 0.6, p < 0.001). Daily dosage of OXN-PR slightly increased (T0: 81.3 ± 6.0; T60: 93.6 ± 34.0; p < 0.001). The impact of pain on QoL abated (p < 0.0001), and bowel function improved overtime (p < 0.001). After the switch to OXN-PR, the number of patients complaining for side effects decreased overall (p < 0.0001); laxatives and antiemetic use also declined significantly.

CONCLUSIONS: OXN-PR was highly effective and well tolerated even at high doses in cancer patients with chronic pain. The agonist-antagonist combination rapidly alleviated pain and its impact on life style, reducing the number of BTCP and improving opioid side effects.