Author:
Nitsche Mirko,Christiansen Hans,Lederer Katinka,Griesinger Frank,Schmidberger Heinz,Pradier Olivier
Abstract
Abstract
Background and purpose
Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation.
Materials and methods
Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m2 per day and increased by steps of 3 mg/m2 per day.
Results
At a daily dose of 16 mg/m2, one out of six patients developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III toxicity was not observed. The dose of 13 mg/m2 was identified as the MTD. All patients developed a fludarabine dose-dependent lymphocytopenia.
Conclusion
Fludarabine can be safely administered concurrently with radiation at a daily dose of 13 mg/m2 during the final 2 weeks of radiotherapy. Further prospective clinical studies are required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of locally advanced inoperable NSCLC.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine
Reference48 articles.
1. Abacioglu U, Yumuk PF, Caglar H, Sengoz M, Turhal NS (2005) Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer. BMC Cancer 5:71
2. Blanco R, Solé J, Montesinos J, Mesia C, Algara M et al. (2008) Induction chemotherapy with cisplatin and gemcitabine followed by concurrent chemoradiation with twice-weekly gemcitabine in unresectable stage III non-small cell lung cancer: final results of a phase II study. Lung Cancer 62(1):62–71
3. Brockman RW, Cheng YC, Schabel FM, Montgomery JA (1980) Metabolism and chemotherapeutic activity of 9-β-d-arabino-furanosyl-2-Fuoroadenine against murine leukemia L1210 and evidence for its phosphorylation by deoxycytidine kinase. Cancer Res 40:3610–3615
4. Buccheri G, Ferrigno D (1996) Therapeutic options for regionally advanced non-small cell lung cancer. Lung Cancer 14:281–300
5. Cheson BD (1995) Infectious and immunosuppressive complications of purine analog therapy. J Clin Oncol 13:2431–2448
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献