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

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Abstract

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.

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Acknowledgements

Editorial assistance for the preparation of this manuscript was provided by Luca Giacomelli, PhD, and Sara Parodi, PhD, on behalf of Content Ed Net; this assistance was funded by Mundipharma Pharmaceuticals srl, Milan Italy.

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Authors and Affiliations

  1. Azienda Ospedaliera Cosenza, UOC Terapia Dolore e Cure Palliative, Via Luigi Sturzo 1, Rogliano, CS, Italy

    Francesco Amato & Silvia Ceniti

  2. Azienda Ospedaliera Cagliari, UO Terapia Dolore, Cagliari, Italy

    Sergio Mameli & Giovanni M. Pisanu

  3. Azienda Ospedaliera Careggi, UO Terapia Dolore, Florence, Italy

    Renato Vellucci

  4. Azienda Ospedaliera Benevento, UO Terapia Dolore, Benevento, Italy

    Vincenzo Palmieri

  5. Azienda Ospedali Riuniti di Foggia, UO Terapia Dolore, Foggia, Italy

    Leonardo Consoletti

  6. Azienda Ospedaliera Piove di Sacco UO Terapia Dolore e Cure Palliative, Padova, Italy

    Dorotea Magaldi

  7. Azienda Ospedaliera Niguarda, UO Terapia Dolore, Milan, Italy

    Paolo Notaro

  8. Istituti Clinici e Scientifici Maugeri, Veruno, Italy

    Claudio Marcassa

Authors
  1. Francesco Amato
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  2. Silvia Ceniti
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  3. Sergio Mameli
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  4. Giovanni M. Pisanu
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  5. Renato Vellucci
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  6. Vincenzo Palmieri
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  7. Leonardo Consoletti
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  8. Dorotea Magaldi
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  9. Paolo Notaro
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  10. Claudio Marcassa
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Corresponding author

Correspondence to Francesco Amato.

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Amato, F., Ceniti, S., Mameli, S. et al. High dosage of a fixed combination oxycodone/naloxone prolonged release: efficacy and tolerability in patients with chronic cancer pain. Support Care Cancer 25, 3051–3058 (2017). https://doi.org/10.1007/s00520-017-3709-5

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  • DOI: https://doi.org/10.1007/s00520-017-3709-5

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