Successful use of ketamine for intractable cancer pain


Goals and work

Despite medical awareness, intractable pain is a serious problem in cancer and occurs in up to 2% of advanced cancer patients. However, few data are available concerning the optimal treatment of such patients. The emergence of intractable pain may notably be due to the activation of N-methyl-D-aspartate (NMDA) receptors located in the central nervous system. NMDA antagonists might thus be an interesting approach in such pain syndromes.

Patients and methods

Twelve patients with intractable cancer pain received a test dose of 5–10 mg of ketamine, a strong NMDA antagonist, in order to determine their response and tolerance to the drug. Continuous intravenous infusions of ketamine associated with morphine were then administered.

Main results

The acute test dose was successful in all cases (VAS <3/10 after 5 min). The prolonged use of ketamine allowed us to reduce the total daily dose of morphine required (range: 200–1,200 mg) by 50% and allowed eight patients to go home with a portable pump with morphine and ketamine during a relatively long period of time (range: 7–350 days, median: 58 days). Side effects were moderate (dizziness) and they were limited to the test phase.


Our data suggest the importance of NMDA receptors in the genesis of chronic cancer pain and indicate that NMDA antagonists should be further studied for the management of cancer pain and, in particular, intractable pain.

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  1. 1.

    Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M (1994) Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain 56:51–57

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Bruera E, Mac Millan K, Hanson J, MacDonald RN (1989) The Edmonton grading system for cancer pain: preliminary report. Pain 37:203–209

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Byas-Smith MG, Max MB, Gracely RH, Bennet GJ (1993) Intravenous ketamine and alfentanil in patients with chronic causalgic pain and allodynia (abstract). 7th World Congress on Pain 454–455

  4. 4.

    Chapman V and Dickenson A H (1992) The combination of NMDA antagonism and morphine produces profound antinociception in the rat dorsal horn. Brain Res 573:321–323

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Dickenson AH (1997) NMDA receptor antagonists: interactions with opioids. Acta Anesthesiol Scand 41:112–115

    CAS  Google Scholar 

  6. 6.

    Fine PG (1999) Low-dose ketamine in the management of opioid nonresponsive terminal cancer pain. J Pain Symptom Manage 14:296–300

    Article  Google Scholar 

  7. 7.

    Foley KM (1985) The treatment of cancer pain. New Engl J Med 313:84–95

    CAS  PubMed  Google Scholar 

  8. 8.

    Klepstadt P, Maurset A, Moberg ER, Oye I (1990) Evidence of a role of NMDA receptors in pain perception. Eur. J. Pharmacol 187:513–518

    Google Scholar 

  9. 9.

    Lossignol DA (1993) Pitfalls in the use of opiates in treatment of cancer pain. Support. Care Cancer 1:256–258

    CAS  Google Scholar 

  10. 10.

    Lossignol DA, Bredas P and Obiols M (1995) Patient controlled analgesia in cancer patients (abstract). Support. Care Cancer 3:356

    Google Scholar 

  11. 11.

    Lossignol DA (1989) Ketamine and morphine in cancer pain: preliminary report. Topics on Supportive Care in Cancer 6–9

    Google Scholar 

  12. 12.

    Maurset A, Skoglund LA, Hustveit O and Oye I (1989) Comparaison of ketamine and pethidine in experimental and postoperative pain. Pain 36:37–41

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Mercadante S, Serreta R, Sapio M, Villari P, Calderone L (1999) When all else fails: stepwise multiple solutions for a complex cancer pain syndrome. Support Care Cancer 7:47–50

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Obbens EAMT, Straton Hill C, Leavens ME, Ruthenbeck SS, Otis F (1987) Intraventricular morphine administration for control of chronic cancer pain. Pain 28:61–68

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Park KM, Max MB, Robinovitz E, Gracely RH, Bennet GJ (1995) Effect of intravenous ketamine, alfentanil, or placebo on pain pinprik hyperalgesia, and allodynia produced by intradermal capsaicin in human subjects. Pain 63:163–172

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Portenoy R K and Hagen NA (1990) Breakthrough pain: Definition, prevalence and characteristics. Pain 41:273–281

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Sethna NF, Liu M, Gracely R, Bennett GJ, Max MB (1998) Analgesic and cognitive effects of intravenous ketamine-alfentanil combinations versus either drug alone after intradermal capsaicin in normal subjects. Anesth Analg 86:1250–1256

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Sosnowsky M, Lossignol DA, Fodderie L (1993) Reversibility of opioid insensitive pain (abstract). 7th World Congress on Pain 16

  19. 19.

    Wagemans MFM, Bakker EN, Zuurmond WWA, Spoelder EN, Loenen AC, De Lange JJ (1995) Intrathecal administration of high-dose morphine solutions decreases the pH of cerebrospinal fluid, Pain 61:55–59

    Google Scholar 

  20. 20.

    White PF, Way WL, Trevor AJ (1982) Ketamine-Its pharmacology and therapeutic uses. Anesthesiology 56:119–136

    CAS  PubMed  Google Scholar 

  21. 21.

    Yamamoto T, Yaksh TL (1992) Studies on the spinal interactio of morphine and the NMDA antagonist MK-801 on the hyperesthesia observed in a rat model sciatic mononeuropathy. Neurosci Lett 135:67–70

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Zech DFJ, Gron S, Lynch J, Hertel D, Lehmann KA (1995) Validation of World Health Organization Guidelines for cancer pain relief: a 10-years prospective study. Pain 63:65–76

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Dominique A. Lossignol.

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Lossignol, D.A., Obiols-Portis, M. & Body, JJ. Successful use of ketamine for intractable cancer pain. Support Care Cancer 13, 188–193 (2005).

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  • Cancer pain
  • Intractable pain
  • Morphine
  • Ketamine