1. 2022;25;E414-E425Rationale and Recent Advances in Targeted Drug Delivery for Cancer Pain: Is It Time to Change the Paradigm?
   Narrative Review
   Denis Dupoiron, MD, Rui Duarte, PhD, Gabriel Carvajal, MD, Frederic Aubrun, PhD, and Sam Eldabe, PhD.

BACKGROUND: Cancer pain prevalence remains high with more than 60% of patients with advanced cancer experiencing cancer-related pain. The undertreatment of pain due to concerns of opioid dependence or diversion, as well as the potential effect of opioids on tumor neogenesis, add to the suffering among cancer populations.

OBJECTIVES: The aim of this narrative review was to assess evidence on the effectiveness, safety, cost-effectiveness, and advances of Intrathecal (IT) Drug Delivery Systems (IDDS) for the management of cancer pain.

STUDY DESIGN: The present review was performed by searching for articles indexed in PubMed, MEDLINE, SciELO, Google Scholar, and Scopus.

METHODS: Studies were included if they investigated patients with chronic cancer-related pain treated with IDDS and assessed experienced pain. We performed a narrative synthesis.

RESULTS: IDDS have demonstrated efficacy in relieving cancer pain even in the challenging treatment of head and neck cancer pain. IDDS is also associated with a large reduction in serum opioid concentrations limiting adverse effects. When combined with other analgesics commonly used in the spinal space, but not systemically, pain relief may be dramatically improved. Advances in IT drug diffusion, including mixtures created with pharmaceutical compounding, improve the safety and accuracy of this therapy. IDDS is cost-effective and safe yet remains underutilized in this patient population.

LIMITATIONS: Despite numerous clinical studies, only a small number of randomized trials have been conducted to evaluate the effectiveness of IDDS for cancer pain.

CONCLUSIONS: This article presents an overview of the current state of evidence on the effectiveness, safety, cost-effectiveness, and advances of IDDS for the management of cancer pain. Despite current evidence, IDDS remains underutilized for people with cancer pain. Potential areas to facilitate its use are discussed. A shift in the paradigm of cancer pain treatment should be considered given the undertreatment rate, lack of benefits, and considerable risks associated with oral opioid medication in many patients who suffer from chronic cancer pain.

KEY WORDS: Cancer pain, intrathecal drug delivery systems, narrative review, opioids, undertreatment