1. ACUTE CANCER PAIN Dr Mike Bennett Senior Clinical Lecturer in Palliative Medicine St Gemma’s Hospice and University of Leeds

2. Overview Epidemiology Presentations Pathophysiology Conventional treatment Unconventional treatment

3. Epidemiology Incidence Cancer pain –50% of patients at diagnosis –>75% in advanced disease Cancer in the UK –150,000 deaths Huge problem

4. Epidemiology Incidence Pain can be caused by –the cancer –the treatment –coexisting diseases –debility

5. Epidemiology Karolinska Institute audit Audit of 153 cancer patients in major hospital 61% had pain, VAS 2.4-6.6 Problems –lack of pain diagnosis –failure to detect neuropathic pain components –under dosing of opioids Arner et al, Lakartidningen 1999

6. Epidemiology Barriers to analgesia 159 cancer pain patients and their carers Variables studied: attitudes to opioids, pain scales, type of analgesia Carer attitude to opioids predicted adequacy of patient analgesia more than patient attitude Lin, Pain 2000

7. Presentations Acute pains –fractures –GI obstruction Acute on chronic –visceral invasion –chest wall disease –bone metastases

8. Presentations Episodic / breakthrough pain –movement related –spontaneous / neuropathic 164 cancer patients with controlled background pain –51% had breakthrough pain –associated with more intense background pain, worse functional impairment and distress Portenoy et al Pain 1999

9. Presentations Escalating –anxiety and fear –rapid disease progression

10. Pathophysiology Clinically –mixed nociceptive and neuropathic –inflammatory At spinal level –can be distinguished from inflammatory and neuropathic pain –features of persistent pain states (greater cfos induction) –CCK and opioid receptor interactions Honore et al Neuroscience 2000

11. Conventional treatment Remember the notion of total pain Best results with a combination of –hard / tangible approaches –soft / intangible approaches

12. Pain management approach

13. Conventional treatment WHO Guidelines WHO ladder 1986 Well tried and tested –Validity studies 1985-1990: –3220 patients –2361 achieved ‘pain control’ (73%) A quarter of all cancer pain patients didn’t achieve pain control Twycross 1994

14. Conventional treatment WHO Guidelines 593 cancer pain patients surveyed Treatment based on opioids +/- adjuvants –36% of patients had neuropathic component –NP no more intense than nociceptive group –66% had strong opioids –43% had adjuvants –VAS decreased from 70mm to 21mm Grond et al, Pain 1999

15. Conventional treatment Steps 1 and 2 Paracetamol COX 2 inhibitors - rofecoxib 25mg daily+ –useful adjunct –no better than paracetamol for bone pain Cocodamol (30/500) 2 tabs qds Moore et al Pain 1997

16. Conventional treatment Step 3 - Opioid titration ‘By the mouth, the clock, the ladder’ Morphine first choice –20-30mg MST bd if exposed to step 2 analgesic –give a 4 hourly dose as breakthrough –increase by 30-50% after 48hrs as required

17. Conventional treatment Opioid switching Based on incomplete cross-tolerance –same analgesia but better side effects Front runners –oxycodone –fentanyl –methadone Also rans –hydromorphone

18. Conventional treatment Adjuvants In neuropathic pain –amitriptyline NNT = about 2 –gabapentin NNT = about 3.5 (but is carbamazepine better?) Not enough data on NNH in cancer patients Wiffen et al Cochrane Reviews 2000 Sindrup and Jenssen Pain 1999

19. Conventional treatment Pamidronate IV bisphosphonate Higher doses used for bone pain –90mg every 4 weeks –60% of patients improve in 14 days –repeat after 4-6 weeks Mannix et al Palliat Med 2000

20. Unconventional treatment Ketamine NMDA antagonist Oral and parenteral Small studies of efficacy in cancer pain –mainly neuropathic Useful adjunct to opioids clinically –but hampered by adverse effects Mercadante JPSM 2000

21. Unconventional treatment Spinal analgesia Systematic review showed no large randomised controlled trials –variable quality evidence –morphine and bupivacaine most widely used Observational study in 43 cancer patients –nociceptive = 77% relief, 66% at 5 months –neuropathic = 66% relief, 11% at 2.5 months Bennett et al JPSM 2000 Becker et al Stereo+Funct Neurosurg 2000

22. Unconventional treatment Oral transmucosal fentanyl Rapid release oral fentanyl on a stick Used for breakthrough pain Similar to parenteral opioid in onset –as good at 1 hour? No relationship between OTFC dose and maintenance analgesia Coluzzi et al Pain 2001

23. Unconventional treatment PCAS Small trials in cancer pain Weakness and frailty limit application 28 cancer patients –PCA until stable then oral morphine –mean duration to pain relief = 5 hours No comparison with oral titration Radbruch et al Clin J Pain 1999

24. Summary Acute cancer pain –big problem –hampered by inadequate assessment and underdosing Treatment –Remember hard and soft approaches –WHO ladder works (and includes adjuvants) –5% need unconventional therapies