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

BACKGROUND: Effective management of severe cancer pain remains challenging. Our phase II study suggested that intravenous patient-controlled analgesia with hydromorphone (IPCA-HM), delivered either as bolus-only or continuous infusion, is superior to oral morphine for patients with severe cancer pain, with bolus-only potentially providing comparable efficacy to infusion while resulting in a lower rate of morphine equivalent dose (MED) escalation. This phase III study aimed to validate these findings. PATIENTS AND METHODS: Patients with solid tumors and severe cancer pain (≥7 at rest on an 11-point Numeric Rating Scale [NRS]) who achieved successful 24-hour IPCA-HM dose-finding were randomized (2:2:1) to bolus-only IPCA-HM (bolus), continuous infusion IPCA-HM (infusion), or oral morphine (oral) for 6 days. The primary outcome was average NRS score over days 1-3 (3DNRS). RESULTS: Of 1,349 patients from 48 oncology centers, 542 received bolus, 540 infusion, and 267 oral. Mean [SD] 3DNRS scores were 2.36 [0.89], 2.26 [0.87], and 2.94 [1.16], respectively. Both IPCA-HM arms were statistically significantly better than the oral arm in 3DNRS scores (bolus vs oral: mean difference, 0.58 [95% CI, 0.42 to 0.74]; infusion vs oral: 0.68 [95% CI, 0.52 to 0.84]; both P