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.
Our patient was a 71 year old woman diagnosed with a high-grade right triceps pleomorphic sarcoma in 2017, which was resected with a wide local excision and treated with adjuvant radiation. A surveillance computed tomography (CT) scan of the thorax showed metastases to the lung and mediastinum in September 2018 and she was treated with 6 cycles of doxorubicin. Progression of disease identified in January 2019 necessitated a change of treatment to ifosfamide and mesna, and she was admitted for each cycle. Re-staging CT scan after 2 cycles demonstrated an interval decrease in the size and number of the multiple pulmonary nodules with one nodule reducing in size from 18 mm down to 6 mm, complete resolution of a 15 mm right para-oesophageal node and no new disease identified.\nPast medical history included hypertension, hysterectomy for menorrhagia and appendectomy. Her medications on admission were lercanidipine, losartan, hydrochlorothiazide, potassium supplement, enoxaparin (thrombosis prophylaxis), senna, domperidone, aprepitant, Fortisip Compact Fibre, Procal Shot, multivitamin and evening primrose oil (not administered due to unknown possible drug interactions). She was known to develop a rash with penicillin but had no other allergies.\nExamination on admission for cycle 3 was remarkable for oral candidiasis. Routine blood investigations identified potassium 2.7 mmol/l which was replaced with IV and oral potassium and albumin of 32 g/l. She developed nausea after day 2 and had one episode of vomiting.\nOn day 3, she was noted to be resting during the morning, however was easily rousable and able to stay awake. Chemotherapy was commenced at midday. Within 4 h, it was noted that she was difficult to rouse. Vital signs were within normal ranges. A blood gas confirmed a potassium of 2.7 mmol/l, but no other abnormality was identified and the pH was uncompensated and in the normal range. An ECG was unremarkable. It was hypothesized that she had developed ifosfamide encephalopathy and an EEG was obtained.