Wednesday, November 12, 2008

Cancer pain research wish lists

BMJ has published evidence-based summary guidelines about the management of cancer pain. Nothing new of course. I found most interesting their recommendations for urgent needs for research:

  • The relation between cancer pain and associated levels of psychological disability and distress
  • Psychosocial interventions that are effective in reducing such disability and distress
  • Standardisation of research methods into complementary therapies and the effect on pain of each individual intervention
  • Determination of the benefits and harms of moving directly from step 1 to step 3 in the WHO ladder in patients with rapidly advancing pain who have never taken opioids before
  • The effectiveness of different opioids and formulations in the management of breakthrough pain
  • The method for determining the most effective dose of breakthrough analgesia for oral opioids such as morphine by comparing doses that are a fixed proportion of the daily regular opioid with a dose titrated to the individual patient or pain
  • Determination of the effect of paracetamol on pain and wellbeing in patients already on a strong opioid regimen
  • The role of ketamine as an adjuvant analgesic
  • The role of topical analgesics, including opioids and topically applied local anaesthetics
  • The value of opioid switching
  • The role of cannabinoids in treating neuropathic pain.
My major response to this is that as much as I love more research as much as the next guy, I thought several of these topics had some good, at least observational data supporting them: opioid switching, breakthrough dose (ok, so it may not have been researched extensively, but lack of trial data telling me what breakthrough dose to start with is not a major clinical issue for me), skipping step 2 of the WHO ladder (does anyone dawdle with step 2 for patients in severe pain anyway?) - I can't remember off the top of my head but I'm sure in the last 5 years someone published research demonstrating that this is safe/fine/good.

I'm thinking through my counter-list of research I'd like to see for cancer-pain and it's something like this (please leave comments with your own, and please recognize this is a spontaneously improvised wish-list and nothing more):
  • A controlled trial of ketamine as a co-analgesic alongside opioids for cancer pain (which involves oral ketamine and outpatients) with persistent moderate to severe pain or intolerable opioid side effects despite a couple weeks of opioid titration (or some similar inclusion criteria)
  • A RCT of sublingual buprenorphine vs. oral morphine for cancer pain in a North American population
  • Same for levorphanol
  • Placebo controlled trials of methylphenidate and modafinil for persistent opioid-related sedation/fatigue
  • A planned, prospective safety and efficacy trial with rigorous safety monitoring of outpatient opioid rotations to methadone in patients with relatively long prognoses (> 6 months)
  • The big adjuvant smack-down pitting gabapentin, pregabalin, a TCA, and an SNRI (e.g. duloxetine) head to head for neuropathic cancer pain which looks at time to acceptable analgesia, safety/tolerance, and cost
  • A large (for palliative care - you know - 50 patients or something) placebo controlled trial of systemic lidocaine for opioid refractory pain
  • Same for mexiletine
  • Long-term safety/efficacy trials for methylnaltrexone (at least monitoring trials) - these may already be going on
  • Lidocaine 5% topical patch vs placebo patch for everything focal
  • More trials defining with whom and when to use spinal opioids (e.g. intrathecal pumps)

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