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

Abstract

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.

Oxaliplatin-Induced Lhermitte’s Phenomenon as a Manifestation of Severe Generalized Neurotoxicity

“…The alterations in peripheral nerve excitability identified in the present study may reflect disruption in DRG excitability, leading in severe cases to the development of Lhermitte’s phenomenon. While an alternate view may suggest a separate pathophysiology underlying hyperexcitability [35], findings from the present study that include more extreme changes in the Lhermitte’s group of patients, would suggest that this phenomenon is an extreme example of DRG neurotoxicity rather than a separate phenomenon. As such, our ongoing work in early preclinical identification of oxaliplatin-induced neurotoxicity aims to prevent the development of such clinical manifestations in the future [36].…”

Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health

“…Although PGB and gabapentin share the same analgesic mechanism exerted through binding to the  2  subunit of N-type voltage-sensitive Ca2+ channels (VSCCs), PGB has a higher affi nity for the subunit, might have additional mechanisms involving the secretory pathway of synaptic vesicles and has a better pharmacokinetic profi le than gabapentin [37]. In addition, as mentioned above, GI tract tumours were the most frequent ones in the group receiving an anticon- vulsant, and it might partially explain the use of PGB, instead of any other anticonvulsant, since there is strong evidence [34][35][36] of its effi cacy in treating chemotherapyinduced pain in GI cancer. The number of analgesic treatments at 8 weeks was signifi cantly larger in the PGB than in the non-PGB group because the fi rst one always had PGB added to whichever other drug or drug combination was being used.…”

“…There is strong evidence, based in animal models [34][35][36], of PGB effi cacy in treating chemotherapy-induced pain in GI cancer. That might be the reason for the use of PGB in patients suffering from this type of tumour.…”

Oxaliplatin-Induced Neuropathy in Colorectal Cancer

“…However, a negative randomised trial suggests lamotrigine is ineffective as treatment for chemotherapy-induced neuropathy [52]. Based on individual case reports and small nonrandomized series, other potential therapeutic options for patients, once large confirmatory studies are done, include gabapentin [60] and pregabalin [60, 61]. …”