levoleucovorin and Hepatic-Encephalopathy

There is no known effective salvage chemotherapy for patients with refractory or relapsed urothelial tumors after methotrexate/cisplatin-based regimen. We report the results of a phase II trial with the FIFO regimen that includes from day 1 to 5: fluorouracil 350 mg/m2, folinic acid 20 mg/m2, and ifosfamide 1000 mg/m2, Q4W. Fifteen patients with metastatic measurable urothelial cancer were enrolled in this trial. Previous therapy included M-VAC regimen in 11 patients, CMV regimen in 3 patients, and both regimens in 1 patient. Thirty-one courses were delivered. Toxicity was moderate, including encephalopathy grade 2 in 2 patients and hematological toxicity grade 3 in 2 others. However, an early death occurred on day 1 in a patient who progressed rapidly and died from hepatic insufficiency after initial encephalopathy. No objective response was seen. Twelve patients progressed during FIFO therapy and 3 patients experienced a stable disease. Despite almost encouraging results of fluorouracil and ifosfamide in the literature, their combination according to our schedule is not active in urothelial cancer.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Transitional Cell; Fluorouracil; Hepatic Encephalopathy; Humans; Ifosfamide; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Retroperitoneal Neoplasms; Salvage Therapy; Treatment Failure; Urologic Neoplasms

We describe nine asymptomatic chronic carriers of hepatitis B virus, four males and five females, with a mean age of forty-six years and all were Chinese, who developed exacerbation of hepatitis following chemotherapy for haematological malignancies. Seven patients had non-Hodgkin's lymphoma of whom three were treated with MACOP-B, two with BCEPP, one with PROMACE-CYTABOM and one with CHOP. Two patients had acute myeloid leukaemia and were treated with daunorubicin and cytosine arabinoside. Exacerbation of hepatitis occurred between one to four weeks following the last course of chemotherapy in eight patients. Two patients developed exacerbation of hepatitis when the dosage of prednisolone was reduced after they had ten weeks of high dose prednisolone. The outcome was fatal in six patients; all of whom developed hepatic encephalopathy. In four of these patients, alanine transaminase levels exceeded 1000 iu/l. Cytotoxic and immunosuppressive therapy permit enhanced viral replication. Withdrawal of the drugs results in partial restoration of immunocompetence and leads to rapid destruction of hepatocytes with consequent hepatic necrosis. Hence, patients who are hepatitis B virus carriers undergoing chemotherapy should be closely monitored. The fatal outcome of reactivation of chronic hepatitis B virus warrants prospective trials addressing preventive measures.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carrier State; Chronic Disease; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Progression; Doxorubicin; Etoposide; Female; Hepatic Encephalopathy; Hepatitis B; Humans; Leucovorin; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Vincristine