This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Postmus, P. E. Articles by Giaccone, G. Search for Related Content PubMed PubMed Citation Articles by Postmus, P. E. Articles by Giaccone, G. Social Bookmarking                            What's this?

Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

From the Departments of Pulmonary Diseases and Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, Departments of Neurology and Pulmonary Diseases, University Hospital, Groningen, and Department of Pulmonary Diseases, Academisch Ziekenhuis Dijkzigt, Rotterdam, the Netherlands; Department of Oncology, University Hospital, Gdansk, and Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Ospedale Regionale, Oncologia Medica, Aosta, Italy; Western General Hospital, Edinburgh, Scotland; and European Organization for the Research and Treatment of Cancer Data Center, Brussels, Belgium.

Address reprint requests to Pieter E. Postmus, MD, PhD, Department of Pulmonary Diseases, University Hospital Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands; email long{at}azvu.nl

PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.

PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m² was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.

RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P < .001). Time to progression in the brain was longer in the combined-modality group (P = .005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P = .087).

CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				B. J. Slotman, M. E. Mauer, A. Bottomley, C. Faivre-Finn, G. W.P.M. Kramer, E. M. Rankin, M. Snee, M. Hatton, P. E. Postmus, L. Collette, et al. Prophylactic Cranial Irradiation in Extensive Disease Small-Cell Lung Cancer: Short-Term Health-Related Quality of Life and Patient Reported Symptoms--Results of an International Phase III Randomized Controlled Trial by the EORTC Radiation Oncology and Lung Cancer Groups J. Clin. Oncol., January 1, 2009; 27(1): 78 - 84. [Abstract] [Full Text] [PDF]

				B. Slotman, C. Faivre-Finn, G. Kramer, E. Rankin, M. Snee, M. Hatton, P. Postmus, L. Collette, E. Musat, S. Senan, et al. Prophylactic Cranial Irradiation in Extensive Small-Cell Lung Cancer N. Engl. J. Med., August 16, 2007; 357(7): 664 - 672. [Abstract] [Full Text] [PDF]

				A. F. Eichler and J. S. Loeffler Multidisciplinary Management of Brain Metastases Oncologist, July 1, 2007; 12(7): 884 - 898. [Abstract] [Full Text] [PDF]

				J. F. Deeken and W. Loscher The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses Clin. Cancer Res., March 15, 2007; 13(6): 1663 - 1674. [Abstract] [Full Text] [PDF]

				T. Seute, P. Leffers, J. T. Wilmink, G. P.M. ten Velde, and A. Twijnstra Response of Asymptomatic Brain Metastases From Small-Cell Lung Cancer to Systemic First-Line Chemotherapy J. Clin. Oncol., May 1, 2006; 24(13): 2079 - 2083. [Abstract] [Full Text] [PDF]

				K. F. Hofland, A. V. Thougaard, M. Dejligbjerg, L. H. Jensen, P. E.G. Kristjansen, P. Rengtved, M. Sehested, and P. B. Jensen Combining Etoposide and Dexrazoxane Synergizes with Radiotherapy and Improves Survival in Mice with Central Nervous System Tumors Clin. Cancer Res., September 15, 2005; 11(18): 6722 - 6729. [Abstract] [Full Text] [PDF]

				N J Pease, A Edwards, and L J Moss Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review Palliative Medicine, June 1, 2005; 19(4): 288 - 299. [Abstract] [PDF]

				C. A. Meyers, J. A. Smith, A. Bezjak, M. P. Mehta, J. Liebmann, T. Illidge, I. Kunkler, J.-M. Caudrelier, P. D. Eisenberg, J. Meerwaldt, et al. Neurocognitive Function and Progression in Patients With Brain Metastases Treated With Whole-Brain Radiation and Motexafin Gadolinium: Results of a Randomized Phase III Trial J. Clin. Oncol., January 1, 2004; 22(1): 157 - 165. [Abstract] [Full Text] [PDF]

				D. Antonadou, M. Paraskevaidis, G. Sarris, N. Coliarakis, I. Economou, P. Karageorgis, and N. Throuvalas Phase II Randomized Trial of Temozolomide and Concurrent Radiotherapy in Patients With Brain Metastases J. Clin. Oncol., September 1, 2002; 20(17): 3644 - 3650. [Abstract] [Full Text] [PDF]

				N. D. Doolittle, L. E. Abrey, N. Ferrari, W. A. Hall, E. R. Laws, R. E. McLendon, L. L. Muldoon, D. Peereboom, D. R. Peterson, C. P. Reynolds, et al. Targeted Delivery in Primary and Metastatic Brain Tumors: Summary Report of the Seventh Annual Meeting of the Blood-Brain Barrier Disruption Consortium Clin. Cancer Res., June 1, 2002; 8(6): 1702 - 1709. [Abstract] [Full Text] [PDF]

				R. Arriagada, T. Le Chevalier, A. Riviere, P. Chomy, I. Monnet, E. Bardet, J. A Santos-Miranda, C. Le Pechoux, M. Tarayre, S. Benhamou, et al. Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients Ann. Onc., May 1, 2002; 13(5): 748 - 754. [Abstract] [Full Text] [PDF]