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 54-year-old, gravida 2, para 2, married woman presented with recurrent epithelial ovarian cancer (endometrioid adenocarcinoma). She had noninsulin dependent diabetes mellitus, diabetic retinopathy, and hypertension. Seven years earlier, she underwent coronary artery bypass grafting due to coronary artery disease.\nThree years ago, she was transferred to our center after laparoscopic bilateral salpingo-oophorectomy which led to a diagnosis of epithelial ovarian cancer. She underwent a debulking operation, including total abdominal hysterectomy and pelvic and paraaortic lymph node dissection, total omentectomy, appendectomy, peritoneal mass excision, and left ureter resection and anastomosis. The tumor was categorized as International Federation of Obstetrics and Gynecology (FIGO) stage IIIc and cytoreductive surgery was suboptimal. Following the surgery, she received 6 cycles of adjuvant chemotherapy with paclitaxel/carboplatin. However, because there was disease progression in this patient, she was further treated with 3 cycles of topotecan, followed by 3 cycles of docetaxel. An abdomino-pelvic computed tomography (CT) scan showed aggravation of disease and her serum carbohydrate antigen 125 (CA-125) concentration was elevated from 534 to 1,270 U/mL. We decided to change her chemotherapy regimen to ifosfamide monotherapy.\nShe was started on ifosfamide 1,200 mg/m2/day, administered via continuous infusion on days 1-3 of each 4 week cycle, along with mesna 300 mg/m2/day. On the third day she received ifosfamide, her mental status worsened, with a change from drowsiness to stupor, followed by disorientation, stereotyped movements, and emotional instability. She had no lateralizing neurologic signs. Her blood test results, including measurements of serum glucose, brain natriuretic peptide, and electrolytes, were normal, and her cerebrospinal fluid was negative for malignant cells. In addition, brain magnetic resonance imaging (MRI) findings were normal. An electroencephalogram showed frequent 1-1.5 Hz periodic or single triphasic waves on both hemispheres (). She was diagnosed with ifosfamide-induced encephalopathy, and her chemotherapy was discontinued immediately. Her neurologic symptoms and signs did not improve. Despite the supportive care, her encephalopathy became aggravated, and she developed ifosfamide-induced acute tubular necrosis. She was discharged without any hope for recovery and died within 1 month.