A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy
Introduction
Nasopharyngeal carcinoma (NPC) of an undifferentiated type is responsive to a wide range of chemotherapeutic agents, with response rates ranging from 38 to 91% using combination chemotherapy in the setting of loco-regional recurrence and/or distant metastases 1, 2, 3, 4, 5, 6, 7, 8, 9. A higher response rate is commonly observed with the use of platinum-based regimens than with non-platinum-based regimens. Although platinum-based regimens, especially the combination of platinum and 5-fluorouracil (5-FU), have been widely adopted as the first-line chemotherapy regimen in the treatment of recurrent NPC, the choice of a second-line regimen in patients with an unsatisfactory response to platinum or in those previously treated in an adjuvant setting by platinum-based chemotherapy remains unclear. Despite a large number of publications addressing the efficacy of different chemotherapy regimens in NPC, very few reports had specifically studied the efficacy of second-line chemotherapy in patients previously treated with platinum-based regimens.
Ifosfamide is an analogue of cyclophosphamide that possesses a spectrum of toxicities and clinical activity different from that of its parent compound. Significant haemorrhagic cystitis was the dose-limiting factor in phase I trials until the introduction of the uroprotective agent mesna. Activity has been demonstrated for ifosfamide in a variety of tumours, including testicular cancer, sarcoma, lymphoma, lung cancer, paediatric tumours, and gynaecological malignancies. Recent studies also demonstrated an activity of ifosfamide in head and neck cancers 10, 11, 12, 13. However, studies of ifosfamide-based chemotherapy in NPC, have been sparse. 5-FU is also active against a wide range of tumours, and in combination with cisplatin, has a high activity in head and neck cancers including NPC. The cytotoxic effect of 5-FU can be enhanced further by modulation using low-dose leucovorin. In this study, we chose to investigate the combination of ifosfamide, 5-FU and leucovorin as a second-line chemotherapy regimen in patients with advanced recurrent NPC pretreated with platinum/5-FU chemotherapy.
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Patient characteristics
Between June 1997 and February 1999, 18 patients with advanced recurrent NPC (loco-regional disease and/or distant metastases) were treated with the study regimen ifosfamide, 5-FU and leucovorin (IFL). The inclusion criteria were: histologically proven NPC (undifferentiated or poorly differentiated carcinoma), completed radical treatment, disease recurrence or progression after previous platinum-based chemotherapy given as part of the primary treatment and/or treatment for recurrence, recurrent
Results
18 patients were recruited into the trial from June 1997 to February 1999 and all were evaluable for toxicity and response. All patients had received previous platinum-based chemotherapy; 3 for neoadjuvant and/or adjuvant treatment, 2 for adjuvant treatment after salvage of earlier recurrences (neck dissection for recurrent neck node in one, and resection of lung metastasis in the other), 2 for both neoadjuvant/adjuvant treatment and recurrence and 11 for recurrence. 13 patients had previously
Discussion
There have been few reports on the use of ifosfamide-based chemotherapy in NPC compared with other head and neck cancers. Liu and colleagues reported using single-agent ifosfamide at a dose of 2 g/m2 for 4 days in 33 patients with recurrent NPC, including 18 chemonaı̈ve patients [14]. 31 patients were evaluable and the overall response rate was 45%, with a complete response rate of 6% and a partial response rate of 39%. Stein and associates combined cisplatin at a dose of 50 mg/m2 with
Acknowledgements
This study was supported by grants from the University of Hong Kong (CRCG Grant No. 10202650/25134/21600/323/01, 10202651/25065/21600/323/01, 337/037/0001, and 335/037/0002) and Asta Medica China Ltd.
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2014, Oral OncologyCitation Excerpt :On the other hand, significantly improved results with oxaliplatin over cisplatin in combination with gemcitabine were not observed [29]. After failing first line platinum doublet chemotherapy, non-platinum monotherapy (capecitabine, gemcitabine, docetaxel) or doublets (gemcitabine and vinorelbine, ifosfamide and 5FU or doxorubicin) are often used and response rates between 20% and 40% are observed. [30–38] Among reports of those phase II studies, patients previously treated with platinum-based chemotherapy as part of the primary treatment were often included with those progressing after first line platinum-based salvage chemotherapy and hence bona fide response rates upon progression from first line chemotherapy were often overstated.
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2012, Oral OncologyCitation Excerpt :Platinum-based chemotherapy is considered the preferred regimen for these patients, with response rates in the range of 50–80% and response duration of approximately 7 months.9–21 However, treatment options for patients after failure of a platinum-based treatment remain unclear although several regimens including gemcitabine, irinotecan, vinorelbine, docetaxel and ifosfamide–doxorubicin have been reported to achieve a response rate of 28–67%.22–29 It is worthwhile to develop an effective salvage regimen to increase tumor control rate and prolong survival in those NPC patients with disease relapse or progression after prior platinum-based chemotherapy.
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2012, Annals of OncologyCitation Excerpt :Combination platinum-based chemotherapy is standard therapy also in patients presenting with metastatic disease [6, 7]. Second-line therapies in patients refractory to platinum-based regimens may also lead to clinical benefit [8–10], which is generally short-lived, although long-term surviving patients with metastatic disease treated with chemotherapy and radiotherapy have been reported [11]. Overall, this finding supports the development of additional forms of treatment of NPC.