Successful amelioration of oxaliplatin-induced hyperexcitability syndrome with the antiepileptic pregabalin in a patient with pancreatic cancer

Cancer Chemother Pharmacol. 2008 Mar;61(3):349-54. doi: 10.1007/s00280-007-0584-7. Epub 2007 Sep 12.

Abstract

Background: Oxaliplatin, a platinum derivative used in the treatment of gastrointestinal cancers, has been associated with sensory neuropathies and, more infrequently, a neuromyotonia-like hyperexcitability syndrome. We present a case of hyperexcitability syndrome that developed during the treatment of pancreatic cancer with oxaliplatin and gemcitabine (GEMOX) that was successfully treated with pregabalin.

Case presentation: A 54-year-old woman was undergoing chemotherapy with gemcitabine and oxaliplatin (GEMOX) for stage II-B pancreatic adenocarcinoma. On the third day of her fourth cycle, she presented with twitching of eyelids and tremors of hands. This twitching started bilaterally on the eyelids, followed by teeth jittering, hand shaking, and slurring of speech. A thorough neurological exam revealed no abnormalities except increased tone of both hands-she had difficulty opening her hand after closing it for a hand-grip. She was given a dose of 1 g of IV magnesium sulfate and 1 g of IV calcium gluconate, and 50 mg of IV diphenhydramine. In addition to reassurance, pregabalin was prescribed for these myotonic symptoms at a dosage of 50 mg by mouth three times daily. Improvement occurred in these symptoms within 12 h and she was almost asymptomatic within 72 h.

Conclusion: Oxaliplatin causes a unique spectrum of acute neurological toxicities that have not been observed in patients receiving either cisplatin or carboplatin. Clinically, sensory alterations are most prominent, particularly cold-induced and perioral paresthesias. Other symptoms, such as cramps, jaw stiffness, voice changes, ptosis, and visual field changes suggest that motor nerves or muscles may also be involved (hyperexcitability). Hyperexcitability syndrome, distinct from cold-induced paresthesias and sensory neuropathy, is a rare complication of oxaliplatin chemotherapy; and up to date no pharmacotherapy has been successful in treating these symptoms. This is the first report of the successful amelioration of this syndrome with the antiepileptic pregabalin.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / complications*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / psychology
  • Adult
  • Anticonvulsants / therapeutic use*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Calcium Gluconate / therapeutic use
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Diphenhydramine / therapeutic use
  • Female
  • Gemcitabine
  • Histamine H1 Antagonists / therapeutic use
  • Humans
  • Magnesium Sulfate / therapeutic use
  • Organoplatinum Compounds / adverse effects*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Pancreatic Neoplasms / complications*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / psychology
  • Pregabalin
  • Psychomotor Agitation / drug therapy*
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Anticonvulsants
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Histamine H1 Antagonists
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Magnesium Sulfate
  • Diphenhydramine
  • Calcium Gluconate
  • Gemcitabine