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 Pappo, A. S. Articles by Vietti, T. Search for Related Content PubMed PubMed Citation Articles by Pappo, A. S. Articles by Vietti, T. Social Bookmarking                            What's this?

Up-Front Window Trial of Topotecan in Previously Untreated Children and Adolescents With Metastatic Rhabdomyosarcoma: An Intergroup Rhabdomyosarcoma Study

From the Intergroup Rhabdomyosarcoma Study Group representing the Children’s Cancer Group, the Pediatric Oncology Group, and the Intergroup Rhabdomyosarcoma Statistical Office, Arcadia, CA.

Address reprint requests to Intergroup Rhabdomyosarcoma Study Group Operations Office, Children’s Oncology Group, 440 E Huntington Dr, No 300, PO Box 60012, Arcadia, CA 91066-6012; email jleeson{at}nccf.org

PURPOSE: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS).

PATIENTS AND METHODS: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m² of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m², dactinomycin 1.5 mg/m², and cyclophosphamide 2.2 g/m² (VAC) and vincristine 1.5 mg/m², topotecan 0.75 mg/m² daily x 5, and cyclophosphamide 250 mg/m² daily x 5. Patients who did not respond to topotecan received continuation therapy with VAC alone.

RESULTS: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival.

CONCLUSION: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.

Members of the Intergroup Rhabdomyosarcoma Study Group are included in the Appendix.

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

This article has been cited by other articles:

				C. A.S. Arndt, J. A. Stoner, D. S. Hawkins, D. A. Rodeberg, A. A. Hayes-Jordan, C. N. Paidas, D. M. Parham, L. A. Teot, M. D. Wharam, J. C. Breneman, et al. Vincristine, Actinomycin, and Cyclophosphamide Compared With Vincristine, Actinomycin, and Cyclophosphamide Alternating With Vincristine, Topotecan, and Cyclophosphamide for Intermediate-Risk Rhabdomyosarcoma: Children's Oncology Group Study D9803 J. Clin. Oncol., November 1, 2009; 27(31): 5182 - 5188. [Abstract] [Full Text] [PDF]

				O. Oberlin, A. Rey, E. Lyden, G. Bisogno, M. C.G. Stevens, W. H. Meyer, M. Carli, and J. R. Anderson Prognostic Factors in Metastatic Rhabdomyosarcomas: Results of a Pooled Analysis From United States and European Cooperative Groups J. Clin. Oncol., May 10, 2008; 26(14): 2384 - 2389. [Abstract] [Full Text] [PDF]

				M. L. Metzger, C. F. Stewart, B. B. Freeman III, C. A. Billups, F. A. Hoffer, J. Wu, M. J. Coppes, R. Grant, M. Chintagumpala, E. A. Mullen, et al. Topotecan Is Active Against Wilms' Tumor: Results of a Multi-Institutional Phase II Study J. Clin. Oncol., July 20, 2007; 25(21): 3130 - 3136. [Abstract] [Full Text] [PDF]

				P. J. Houghton and C. L. Morton Rational Use of Human Tumor Xenografts for Drug Development Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 77 - 82. [Full Text] [PDF]

				A. S. Pappo, E. Lyden, P. Breitfeld, S. S. Donaldson, E. Wiener, D. Parham, K. R. Crews, P. Houghton, and W. H. Meyer Two Consecutive Phase II Window Trials of Irinotecan Alone or in Combination With Vincristine for the Treatment of Metastatic Rhabdomyosarcoma: The Children's Oncology Group J. Clin. Oncol., February 1, 2007; 25(4): 362 - 369. [Abstract] [Full Text] [PDF]

				J. J. Lager, E. R. Lyden, J. R. Anderson, A. S. Pappo, W. H. Meyer, and P. P. Breitfeld Pooled Analysis of Phase II Window Studies in Children With Contemporary High-Risk Metastatic Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group J. Clin. Oncol., July 20, 2006; 24(21): 3415 - 3422. [Abstract] [Full Text] [PDF]

				M. L. Bernstein, M. Devidas, D. Lafreniere, A.-K. Souid, P. A. Meyers, M. Gebhardt, K. Stine, R. Nicholas, E. J. Perlman, R. Dubowy, et al. Intensive Therapy With Growth Factor Support for Patients With Ewing Tumor Metastatic at Diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--A Report From the Children's Oncology Group J. Clin. Oncol., January 1, 2006; 24(1): 152 - 159. [Abstract] [Full Text] [PDF]

				P. P. Breitfeld and W. H. Meyer Rhabdomyosarcoma: New Windows of Opportunity Oncologist, August 1, 2005; 10(7): 518 - 527. [Abstract] [Full Text] [PDF]

				P. J. Houghton Human Tumor Xenografts as Preclinical Models: Value and Limitations Am. Assoc. Cancer Res. Educ. Book, April 1, 2005; 2005(1): 33 - 37. [Full Text] [PDF]

				C. S. Kretschmar, M. Kletzel, K. Murray, P. Thorner, V. Joshi, R. Marcus, E. I. Smith, W. B. London, and R. Castleberry Response to Paclitaxel, Topotecan, and Topotecan-Cyclophosphamide in Children With Untreated Disseminated Neuroblastoma Treated in an Upfront Phase II Investigational Window: A Pediatric Oncology Group Study J. Clin. Oncol., October 15, 2004; 22(20): 4119 - 4126. [Abstract] [Full Text] [PDF]

				C. F. Stewart, M. Leggas, J. D. Schuetz, J. C. Panetta, P. J. Cheshire, J. Peterson, N. Daw, J. J. Jenkins III, R. Gilbertson, G. S. Germain, et al. Gefitinib Enhances the Antitumor Activity and Oral Bioavailability of Irinotecan in Mice Cancer Res., October 15, 2004; 64(20): 7491 - 7499. [Abstract] [Full Text] [PDF]

				C. F. Stewart, L. C. Iacono, M. Chintagumpala, S. J. Kellie, D. Ashley, W.C. Zamboni, M.N. Kirstein, M. Fouladi, L. G. Seele, D. Wallace, et al. Results of a Phase II Upfront Window of Pharmacokinetically Guided Topotecan in High-Risk Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumor J. Clin. Oncol., August 15, 2004; 22(16): 3357 - 3365. [Abstract] [Full Text] [PDF]

				D. O. Walterhouse, E. R. Lyden, P. P. Breitfeld, S. J. Qualman, M. D. Wharam, and W. H. Meyer Efficacy of Topotecan and Cyclophosphamide Given in a Phase II Window Trial in Children With Newly Diagnosed Metastatic Rhabdomyosarcoma: A Children's Oncology Group Study J. Clin. Oncol., April 15, 2004; 22(8): 1398 - 1403. [Abstract] [Full Text] [PDF]

				B. J. Weigel, D. A. Rodeberg, A. M. Krieg, and B. R. Blazar CpG Oligodeoxynucleotides Potentiate the Antitumor Effects of Chemotherapy or Tumor Resection in an Orthotopic Murine Model of Rhabdomyosarcoma Clin. Cancer Res., August 1, 2003; 9(8): 3105 - 3114. [Abstract] [Full Text] [PDF]

				J. C. Breneman, E. Lyden, A. S. Pappo, M. P. Link, J. R. Anderson, D. M. Parham, S. J. Qualman, M. D. Wharam, S. S. Donaldson, H. M. Maurer, et al. Prognostic Factors and Clinical Outcomes in Children and Adolescents With Metastatic Rhabdomyosarcoma--A Report From the Intergroup Rhabdomyosarcoma Study IV J. Clin. Oncol., January 1, 2003; 21(1): 78 - 84. [Abstract] [Full Text] [PDF]

				P. J. Houghton, P. C. Adamson, S. Blaney, H. A. Fine, R. Gorlick, M. Haber, L. Helman, S. Hirschfeld, M. G. Hollingshead, M. A. Israel, et al. Testing of New Agents in Childhood Cancer Preclinical Models: Meeting Summary Clin. Cancer Res., December 1, 2002; 8(12): 3646 - 3657. [Abstract] [Full Text] [PDF]

				L. Bomgaars, S. L. Berg, and S. M. Blaney The Development of Camptothecin Analogs in Childhood Cancers Oncologist, December 1, 2001; 6(6): 506 - 516. [Abstract] [Full Text] [PDF]

				W. M. Crist, J. R. Anderson, J. L. Meza, C. Fryer, R. B. Raney, F. B. Ruymann, J. Breneman, S. J. Qualman, E. Wiener, M. Wharam, et al. Intergroup Rhabdomyosarcoma Study-IV: Results for Patients With Nonmetastatic Disease J. Clin. Oncol., June 15, 2001; 19(12): 3091 - 3102. [Abstract] [Full Text] [PDF]