Triple Intrathecal Combination Therapy for End-Stage Cancer-Related Refractory Pain: A Prospective Observational Study with Two-Month Follow-Up

Introduction: In cancer-related pain refractory to systemic opioids, intrathecal (IT) administra- tion of morphine can be a useful strategy. In clinical practice, IT morphine is usually combined with other drugs with different mechanisms of action, in order to obtain a synergistic analgesic effect. However, the discussion on efficacy and safety of IT combination therapy is still ongoing. The aim of this observational study was to report the effects of an IT combination of low doses of ziconotide, morphine, and levobupivacaine in end-stage cancer refractory pain. Methods: Sixty adult patients, 21 females and 39 males, were enrolled to an IT device implant. The mean visual analogue scale of pain inten- sity (VASPI) score was 88 ± 20 mm. All patients started with a triple combination therapy: the initial IT dose of morphine was calculated for each patient based on the equivalent daily dose of morphine; an oral/IT ratio of 400/1 was used. For ziconotide, a standard slow titration sched- ule was started at 1.2 lg/day and the initial dose of levobupivacaine was 3 mg/day. Results: The initial IT mean doses of morphine, ziconotide, and levobupivacaine were 0.8 ± 0.3 mg/day, 1.2 mcg/day and 3 mg/day, respectively. At day 2, a significant reduction in VASPI score was registered (49 ± 17, p 0.001), and this significant reduction persisted at 56 days (mean VASPI score 44 ± 9, p 0.001), with mean doses of morphine 2 ± 1 mg/day, ziconotide 2.8 ± 1 mcg/day, and levobupiva- caine 3.8 ± 2 mg/day. Very few adverse effects (AEs) were observed. Patients’ satisfaction was very high during the entire study period. Conclusions: Our results, within the limit of the study design, suggest that the IT combina- tion of ziconotide, morphine, and levobupiva- caine, at low doses, allows safe and rapid control of refractory cancer pain, with high levels of patient satisfaction.