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.
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.