A 47-year-old African American male with stage III cutaneous T-cell lymphoma with large cell transformation presented to the hospital with shortness of breath, fatigue, and failure to thrive. The patient had progressed through multiple lines of chemotherapy including EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), romidepsin, gemcitabine, brentuximab, and pralatrexate. At inpatient presentation, he had malignant pleural effusions, hypercalcemia, and leukocytosis with eosinophilia. Given the patient’s rapidly worsening clinical course, it was decided to start ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with etoposide 100 mg/m2 on days 1 to 3, ifosfamide 5000 mg/ on day 2 infused over 24 hours, and carboplatin with an area under curve (AUC) of 5 on day 3. He was alert and oriented prior to and during the infusion but became delirious on day 3 of the regimen, 6 hours after the completion of the ifosfamide infusion. Physical examination did not reveal any stereotypical movements or twitching. His mental status worsened from initial agitation and confusion to drowsiness and eventually stupor. Diagnostic evaluation for acute mental status change including complete blood count, comprehensive metabolic panel, ammonia level, and computed tomography scan of the head was negative. Infectious workup including blood cultures, urine culture, and chest X-ray did not reveal any infectious process contributing to the altered mental status. Thus, the patient’s acute altered mental status was attributed to IME. He was started on hydration, and 50 mg of intravenous MB was given every 4 hours. His mental status began to improve 16 hours after start of MB and was back to his baseline after 48 hours of treatment (received 12 total doses). The one cycle of ICE chemotherapy temporarily improved his disease but due to neurotoxicity, he was not rechallenged.
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.