Ziconotide for Severe Neuropathic Pain in Metastatic Breast Cancer

ABSTRACT

The role of ziconotide in managing severe, neuropathic cancer pain is described. This is illustrated by a case of a 63-year-old woman with breast cancer who had failed more conservative therapy but who responded to intrathecal ziconotide. Clinical efficacy and adverse effects of the drug are discussed. Commentaries on this case from the United Kingdom are provided by pain specialists from Spain and The Netherlands.

The content of this case report appeared in: Wells CD (editor). Proceedings of the 3rd International Congress on Neuropathic Pain. NeuPSIG. Athens (Greece), May 27–30, 2010. Pianoro, Italy, Medimond Srl, 2010. ©MedimondSrl. Reproduced with permission. This feature is adapted from paineurope 2012; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

KEYWORDS :

• cancer
• intrathecal
• neuropathic
• pain
• ziconotide

COMMENTARY FROM SPAIN

Hermann Ribera¹

Ziconotide is the first drug expressly developed for administration by the intrathecal (IT) route and it also has been recommended as a first-line IT treatment option for patients with chronic pain.¹ Its advantages, compared with opioids, include an absence of dependence and tolerance, no spinal catheter-tip granulomas and that it does not induce hormonal changes or immunosuppression. The main disadvantages of ziconotide are its most common adverse events: altered mood, confusion, memory deficit, vertigo, and nausea, which can be reduced by slow titration or will disappear a few days after discontinuation.²

In this case, IT ziconotide was necessary and highly satisfactory. Nonetheless, there are alternatives to take into account: firstly, IT morphine (perhaps at higher than usual doses) alone or in combination with bupivacaine +/− clonidine could have been adequate unless IV or SC morphine was shown to ineffective. This is because IT therapy has been associated with greater pain relief with lower doses of drug(s) and with a lower incidence of adverse events. Secondly, because of the presence of neuropathic pain in both lower limbs, spinal cord stimulation could have been attempted. When the patient was readmitted to hospital with confusion and depression, stopping the pump was the best option to ascertain if these symptoms were caused by ziconotide or something else.

COMMENTARY FROM THE NETHERLANDS

Jan H. Vranken²

Most cancer patients with pain can be managed with a combination of nonopioid and opioid drugs.¹ In patients with poor pain control despite oral, IV, or SC drug therapy, intrathecal (IT) administration of analgesics can result in adequate pain relief.² Combinations of morphine with local anesthetics (bupivacaine) have been advocated for IT use in the management of severe intractable pain syndromes, and to prevent excitatory phenomena associated with high escalating IT morphine doses. Alternatively, ziconotide is recommended as a first-line IT therapy for nociceptive, mixed, and neuropathic pain.³ However, it is not without adverse effects, including abnormal gait, memory impairment, dizziness, confusion, nausea, nystagmus, and pain, especially following fast titration and higher dosages. Low starting dosage and slow titration can help improve its safety profile. Ziconotide appears to be an effective IT analgesic for long-term treatment of patients with chronic severe pain. However, it has a narrow therapeutic window because of substantial central nervous system (CNS) side effects. Thus, ziconotide therapy is appropriate for only a small subset of patients. Additional studies evaluating its long-term efficacy and safety for neuropathic pain may be warranted.

KEY LEARNING POINTS

• Ziconotide is a selective N-type voltage-sensitive calcium channel blocker approved for severe chronic pain in adult patients requiring intrathecal analgesia.

Its adverse effects include abnormal gait, memory impairment, dizziness, and confusion, although it is not associated with some side effects characteristic of opioids such as immunosuppression.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes

1 Dr. Hermann Ribera is Director of the Pain Unit, Hospital Universatari Son Espases, Palma de Mallorca, Spain.

2 Jan H. Vranken, MD, PhD, is an anaesthesiologist and coordinator of the Pain Relief Unit, Department of Anaesthesiology, Medical Center Alkmaar, Alkmaar, The Netherlands.