Randomised Phase II Trial (NCT00637975) Evaluating Activity and Toxicity of Two Different Escalating Strategies for Pregabalin and Oxycodone Combination Therapy for Neuropathic Pain in Cancer Patients

Marina Chiara Garassino, Sheila Piva, Nicla la Verde, Ilaria Spagnoletti, Vittorio Iorno, Claudia Carbone, Antonio Febbraro, Anna Bianchi, Annalisa Bramati, Anna Moretti, Monica Ganzinelli, Mirko Marabese, Marta Gentili, Valter Torri, Gabriella Farina

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Abstract

Purpose:Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods:Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. Results:More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. Conclusions: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration: ClinicalTrials.gov NCT00637975.

Original languageEnglish
Article numbere59981
JournalPLoS One
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 5 2013

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Oxycodone
Neuralgia
Toxicity
pain
toxicity
Pain
therapeutics
neoplasms
dosage
Neoplasms
Confusion
rating scales
Sleep Stages
Constipation
Therapeutics
Pruritus
endpoints
Analgesia
Nausea
Opioid Analgesics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Randomised Phase II Trial (NCT00637975) Evaluating Activity and Toxicity of Two Different Escalating Strategies for Pregabalin and Oxycodone Combination Therapy for Neuropathic Pain in Cancer Patients. / Garassino, Marina Chiara; Piva, Sheila; la Verde, Nicla; Spagnoletti, Ilaria; Iorno, Vittorio; Carbone, Claudia; Febbraro, Antonio; Bianchi, Anna; Bramati, Annalisa; Moretti, Anna; Ganzinelli, Monica; Marabese, Mirko; Gentili, Marta; Torri, Valter; Farina, Gabriella.

In: PLoS One, Vol. 8, No. 4, e59981, 05.04.2013.

Research output: Contribution to journalArticle

Garassino, Marina Chiara ; Piva, Sheila ; la Verde, Nicla ; Spagnoletti, Ilaria ; Iorno, Vittorio ; Carbone, Claudia ; Febbraro, Antonio ; Bianchi, Anna ; Bramati, Annalisa ; Moretti, Anna ; Ganzinelli, Monica ; Marabese, Mirko ; Gentili, Marta ; Torri, Valter ; Farina, Gabriella. / Randomised Phase II Trial (NCT00637975) Evaluating Activity and Toxicity of Two Different Escalating Strategies for Pregabalin and Oxycodone Combination Therapy for Neuropathic Pain in Cancer Patients. In: PLoS One. 2013 ; Vol. 8, No. 4.
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abstract = "Purpose:Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods:Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90{\%} probability of detecting the best strategy for a true difference of at least 15{\%}. Results:More patients in arm A (76{\%}) than arm B (64{\%}) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8{\%} vs. 66.7{\%}; nausea: 27.8{\%} vs. 44.4{\%}; drowsiness: 44.4{\%} vs. 55.6{\%}; confusion: 16.7{\%} vs. 27.8{\%}; itching: 8.3{\%} vs. 19.4{\%}. Conclusions: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration: ClinicalTrials.gov NCT00637975.",
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AU - Garassino, Marina Chiara

AU - Piva, Sheila

AU - la Verde, Nicla

AU - Spagnoletti, Ilaria

AU - Iorno, Vittorio

AU - Carbone, Claudia

AU - Febbraro, Antonio

AU - Bianchi, Anna

AU - Bramati, Annalisa

AU - Moretti, Anna

AU - Ganzinelli, Monica

AU - Marabese, Mirko

AU - Gentili, Marta

AU - Torri, Valter

AU - Farina, Gabriella

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N2 - Purpose:Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods:Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. Results:More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. Conclusions: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration: ClinicalTrials.gov NCT00637975.

AB - Purpose:Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods:Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. Results:More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. Conclusions: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration: ClinicalTrials.gov NCT00637975.

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