Use Of Ifosfamide Research Articles

Methylene Blue for Ifosfamide-Associated Encephalopathy

To the Editor: Ifosfamide is a chemotherapeutic agent used in the treatment of cervical carcinoma, soft-tissue sarcomas, and germ-cell tumors. Myelosuppression is common. Hemorrhagic cystitis is prevented by the administration of mesna. Confusion and coma have been associated with the use of ifosfamide, and antiepileptic drugs may be required.1 Ifosfamide may also cause a dose-dependent encephalopathy in the presence of a pelvic mass that obstructs the ureters or intrinsic renal impairment.2 The drug is marketed in the United States as Ifex (Bristol-Myers Oncology Division, Princeton, N.J.). We report the reversal of ifosfamide-associated encephalopathy with methylene blue in a 68-year-old woman . . .

Ifosfamide, mesna, and nephrotoxicity in children.

With the increasing use of ifosfamide in pediatric malignancies, nephrotoxicity has emerged as a potentially serious adverse effect, which may be dose-limiting or may cause severe chronic morbidity, including glomerular impairment and/or Fanconi's syndrome. The purpose of this review was (1) to improve the documentation of ifosfamide nephrotoxicity in children, and (2) to consider the possible causative role of ifosfamide metabolites. (1) A grading system was developed that allowed documentation of the nature and severity of published reports of ifosfamide-induced nephrotoxicity, and evaluation of patient and treatment-related risk factors. (2) The relationship between the pharmacology of ifosfamide/mesna and nephrotoxicity was investigated by examination of published data, especially that concerning the quantitative differences in the metabolism of ifosfamide and its nonnephrotoxic structural isomer, cyclophosphamide. (1) Examination of 16 published reports (with assessable data from 40 children) demonstrated that ifosfamide-induced nephrotoxicity was associated with a wide range of patient ages and ifosfamide cumulative doses given by different administration schedules. (2) Chloroacetaldehyde, a major metabolite of ifosfamide only, may be at least partly responsible for the renal toxicity of this drug. Although mesna may be capable of detoxifying the toxic metabolite(s), delivery to the renal tubule may not be sufficient to provide adequate protection of tubular glutathione from depletion by the metabolite(s), which results in a failure to prevent nephrotoxicity. Increased understanding of the interindividual variability in the extent and nature of ifosfamide metabolism, which may be a major determinant of susceptibility to renal damage, may lead to improved use of the drug with less nephrotoxicity.

Use of ifosfamide in the management of breast cancer.

Ifosfamide, a cytostatic drug highly active in vivo, has slight superiority over cyclophosphamide. It proved effective in experimental tumor systems including the C3H mammary carcinoma. Clinical studies of ifosfamide as monotherapy in breast cancer, begun in 1974 by Ahmann et al., reported a 20% objective response. Subsequent trials were conducted from 1974 through 1977 using ifosfamide as monotherapy, and ifosfamide was also combined with other chemotherapeutic agents. In 1975, Hartwich and coworkers used the combination ifosfamide/vincristine with a 25% overall response. With the introduction of the uroprotector mesna, more studies were instituted. In 1984, using the IMF combination (ifosfamide/methotrexate/5-fluorouracil), we reported a 25% overall response. Other groups also reported good results for ifosfamide-containing combinations, with overall responses ranging from 25% to 79%. Recently, Sanchiz and Milla used high-dose ifosfamide to treat metastatic breast cancer, with a 40% overall response. In conclusion, ifosfamide's efficacy in breast cancer has been confirmed and the drug is highly recommended in combination chemotherapy as a first-line treatment.

Ifosfamide alone and in combination in the treatment of refractory malignant gestational trophoblastic disease

We attempted to evaluate the use of ifosfamide either alone or in combination in patients with refractory malignant gestational trophoblastic disease. Our study comprised, in part, a phase II multiinstitutional trial of ifosfamide in refractory gynecologic malignancies and, in part, a review of institutional experience with ifosfamide in combination chemotherapy. Single-agent ifosfamide produced a significant response in titer in one of two patients with refractory choriocarcinoma. Ifosfamide with etoposide and cisplatin (also known as VIP) resulted in significant response in human chorionic gonadotropin titers in three patients with highly refractory metastatic gestational trophoblastic disease and one cure in this group of patients. Ifosfamide has activity in refractory choriocarcinoma and, when combined with etoposide and cisplatin (VIP), may be curative.