A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy

The aim of this study was to evaluate the efficacy and toxicity of ifosfami de, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherap y regimen in patients with recurrent undifferentiated nasopharyngeal carcin oma (NPC) previously treated with platinum/5-FU. Between June 1997 and Febr uary 1999, 18 patients were entered into the study. 3 patients had loco-reg ional recurrence. 13 had distant metastases and 3 had both loco-regional re currence and distant metastases. All patients had previously received plati num/5-FU as adjuvant or palliative treatments. The IFL regimen consisting o f ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg /m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (r ange: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall r esponse rate of 56% (95% confidence interval(CI): 32-80%). For those patien ts who responded to IFL, 8 had subsequent disease progression on followup, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% Ci: 4.7-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia , although IFL was discontinued in 1 patient because of persisting thromboc ytopenia. IFL is an effective second-line regimen in patients with recurren t NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemonaive patients may further improve the overall response rate and du ration and is worth investigating in future trials. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.