Moffitt Oncology report: Ifosfamide neurotoxicity

Deep gratitude to the Moffitteers for welcoming me at report this morning!
Thank you to Sahil for presenting a case of a woman presenting for AIM chemotherapy who developed acute AMS found to have ifosfamide neurotoxicity.
Top pearls
  • patients who receive ifofamide have a 10-30% incidence of neurotoxicity,
  • most common manifestation are confusion and myoclonus
  • treated with cessation of ifosfamide and methylene blue
What is ifosfamide
  • mechanism: its a fluoropyramidine chemotherapy agent. It alkylates DNA, causing it to cross-link and induce cell death.
  • indications
    • Mostly sarcomas, germ cell tumors, lymphomas
    • stage IV testicular cancer
      • regimens: VIP, VeIP, TIP and TICE
    • soft tissue sarcomas, osteosarcoma and Ewings sarcoma
      • regimens: AIM, ICE and MAID (or-single agent)
      • We see a lot of these rare tumors at Moffit given the sarcoma expertise of the oncology division
    • non-hodgkins lymphoma
      • CODOC-M/IVAC or RICE
    • relapsed or refractory non-hodgkins lymphoma
      • ICE, IGEV
    • Also used as salvage therapy in many other cancer types
  • Epidemiology
    • 10-30% incidence!
      • more common in patients with low serum albumin, renal dysfunction and/or prior nephrectomy, and a history of prior neurotoxicity. Aprepitant, the anti-emetic can also pre-dispose
      • more common with higher cumulative doses
  • Clinical presentation
    • onset hours to days after ifosfamide administration
    • most common symptom is confusion and myoclonus
    • other presenting sx
      • coma
      • agitation
      • non-convulsive status epilepticus
      • ataxia and cerebellar sx
      • weakness and cranial nerve dysfunction
      • hemiballismus (rare)
  • Treatment
    • important to evaluate for other causes of AMS – especially stroke, seizure and infection
    • stop the ifosfamide
    • administer methylene blue
      • Occasionally, this completely reverses the encephalopathy.
      • dexmetatomadine has also been reported to be effective
    • give methylene blue prophylaxis with subsequent rounds of ifosfamide chemo
     Sioka C1, Kyritsis AP. Central and peripheral nervous system toxicity of common chemotherapeutic agents.Cancer Chemother Pharmacol. 2009 Apr;63(5):761-7
Zulian GB, Tullen E, Maton B. Methylene blue for ifosfamide-associated encephalopathy. N Engl J Med. 1995 May 4;332(18):1239-40.

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