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.
A 39-year-old woman had a surgical resection for a uterine leiomyosarcoma in February 2011. A local relapse was treated by resection in March 2012, and the patient was referred for adjuvant chemotherapy in May 2012. Because of the deterioration of her general condition due to an early local relapse, she received first doxorubicin 75 mg/m2 alone. Improvement of her general condition allowed for a combined treatment with doxorubicin (60 mg/m2) and IFO (9 g/m2) for the next 4 cycles. In the 5th and 6th cycles, IFO alone was used because of the cumulative dose of anthracyclines (adjuvant epirubicin had previously been given for a breast cancer). A partial response was obtained, but the tumor remained unresectable and a therapeutic break was decided. In February 2013, CT scan showed progression, and IFO (5 g/m2/day) was started again. Aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) was given with steroids to prevent nausea. Within a few hours after the 2nd cycle, the patient had obnubilation and awareness troubles without any other symptoms. These troubles did not improve with the evacuation of a vesical globe or the cessation of neurodepressing drugs (oxycodone and chlorpromazine). There was no hydroelectrolytic disorder. Encephalic MRI did not show bleeding or a cerebrovascular event. IFO-induced encephalopathy was suspected, and a treatment with methylene blue was started. Improved awareness was transiently observed, but the patient remained disoriented and died 8 days later, without return to normal consciousness.