Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial

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  • 1 Gastrointestinal Medical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou;
  • | 2 College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou;
  • | 3 Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou;
  • | 4 Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou;
  • | 5 Medical Oncology, Quanzhou First Hospital, Quanzhou;
  • | 6 Medical Oncology, Qinghai University Affiliated Hospital, Xining;
  • | 7 Medical Oncology, Xiamen Humanity Hospital & Fujian Medical University Xiamen Humanity Hospital, Xiamen;
  • | 8 Medical Oncology, Yichang Central People’s Hospital, Yichang;
  • | 9 Medical Oncology, Liuzhou Workers’ Hospital, Liuzhou;
  • | 10 Pain Medicine, Cancer Hospital Affiliated with Harbin Medical University, Harbin;
  • | 11 Pain Medicine, Hainan Cancer Hospital, Haikou;
  • | 12 School of Public Health, Fujian Medical University, Fuzhou;
  • | 13 Medical Oncology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi; and
  • | 14 Thoracic Oncology, Fujian Cancer Hospital, Fuzhou, China.

Background: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. Methods: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. Results: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. Conclusions: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.

Submitted March 6, 2022; final revision received May 14, 2022; accepted for publication May 16, 2022.

Author contributions: Study concept and design: R. Lin, Huang. Provision of study material or patients: R. Lin, Zhu, Luo, Lv, Lu, Chen, Zou, Zhang, Wu, Li, Zhou, Zhao, Su, Liu. Administrative support: R. Lin, Liu, Huang. Data collection and assembly: R. Lin, Zhou, Zhao. Data analysis and interpretation: R. Lin, S. Lin, Zhao, Huang. Manuscript writing: All authors. Final approval of manuscript: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the Fujian Cancer Hospital (R. Lin).

Correspondence: Cheng Huang, MD, Thoracic Oncology, Fujian Cancer Hospital, No. 420 Fuma Road, Jinan District, Fuzhou, 350014, China. Email: cheng671@sina.com; and Jiang Liu, MD, Medical Oncology, People's Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Tianshan District, Urumqi, 830002, China. Email: liujiang@csco.org.cn

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