A 38-year-old African American female with refractory stage IV mycosis fungoides with large cell transformation was admitted to the hospital for initiation of ICE chemotherapy. Patient had extensive cutaneous and muscle involvement of the lymphoma and had failed multiple lines of chemotherapy regimens including romidepsin and rituximab, brentuximab, and gemcitabine. Laboratory testing prior to initiation of ICE therapy was normal except for low serum albumin level of 1.7 g/dL. Patient received ICE therapy with etoposide 100 mg/m2 on days 1 to 3, ifosfamide 5000 mg/m2 on day 2 infused over 24 hours, and carboplatin with an AUC of 5 on day 3. She was premedicated with aprepitant for prevention of nausea. She was alert and oriented prior to and during the infusion but became lethargic, somnolent, and confused within 6 to 8 hours of completion of ifosfamide infusion. Physical examination was significant for random jerky movements of both upper and lower extremities, twitching of the right eye, and somnolence. The patient’s evaluation for sudden neurological changes included complete blood count, comprehensive metabolic panel, computed tomography scan of the head, and infectious workup (blood cultures, urine culture, and chest X-ray), all of which were negative. She received naloxone with no reversal of mental status changes. Based on the timing of the infusion and change in mental status, patient was diagnosed with IME and MB was immediately initiated at a dose of 50 mg every 4 hours. An improvement in the patient’s mental status was noticed within 12 hours of initiation of MB, and the patient was back to her baseline in 72 hours (received 18 total doses). Given the neurotoxicity, patient was not rechallenged with ifosfamide and was switched to a different chemotherapeutic regimen.
A 46-year-old, gravida 2, para 2, married woman with recurrent epithelial ovarian cancer (serous adenocarcinoma) was referred to our institution for further management. She had no specific medical history.\nAt initial diagnosis of epithelial ovarian cancer, she underwent bilateral salpingo-oophorectomy, partial omentectomy and incidental appendectomy at another hospital, and cytoreductive surgery was suboptimal. She received 12 cycles of adjuvant chemotherapy with paclitaxel and carboplatin. However, an abdomino-pelvic CT scan showed residual peritoneal carcinomatosis and her serum CA-125 concentration was elevated, from 517 to 1,020 U/mL. After referral to our center, she underwent optimal cytoreductive surgery, including total abdominal hysterectomy, pelvic and paraaortic lymph node dissection, low anterior resection, and right diaphragmatic stripping. After surgery, she received 3 cycles of adjuvant chemotherapy with topotecan and cisplatin. Due to disease progression, her regimen was switched to 3 cycles of docetaxel and carboplatin. Due to the disease progression on this regimen, we changed her chemotherapy regimen to a combination of ifosfamide and etoposide. She received the first cycle of etoposide (75 mg/m2/day in 3-hour infusions on days 1-5) and ifosfamide (1,200 mg/m2/day in 3-hour infusions on days 1-5), along with 300 mg/m2/day mesna, without any complications. On day 6, her speech became unintelligible but her orientation was intact. On day 7, she developed delirium, disorientation, visual and auditory hallucinations, stereotyped movements, and emotional instability. At that time, her estimated glomerular filtration rate, serum creatinine and blood urea nitrogen were 27 mL/min (normal, >60 mL/min), 2.3 mg/dL (normal, 0.7 to 1.4 mg/dL) and 33 mg/dL (normal, 10 to 26 mg/dL), respectively, and her renal function decreased gradually. Brain MRI was normal. After referral to a nephrologist, her electrolyte imbalance was corrected and her uremia was improved by hemodialysis. However, her mental impairments showed no improvement. She was diagnosed as having severe ifosfamide-induced encephalopathy. She never recovered and was discharged in a hopeless condition on day 10 and died within 1 month.