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.
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.