This Article Full Text Full Text (PDF) Erratum (v22,p3434) 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 Arndt, C. Articles by Meyer, W. Search for Related Content PubMed PubMed Citation Articles by Arndt, C. Articles by Meyer, W. Social Bookmarking                            What's this?

Age Is a Risk Factor for Chemotherapy-Induced Hepatopathy With Vincristine, Dactinomycin, and Cyclophosphamide

From the Mayo Clinic, Rochester, MN; Children's Hospital and Regional Medical Center, Seattle, WA; University of Nebraska Medical Center, Omaha, NE; Duke University Medical Center, Durham, NC; Children's Hospital of Philadelphia, Philadelphia, PA; University of Oklahoma Health Sciences Center, Oklahoma City, OK; and Soft Tissue Sarcoma Committee of the Children's Oncology Group, Arcadia, CA.

Address reprint requests to Carola A.S. Arndt, MD, Department of Pediatric Hematology/Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: carndt{at}mayo.edu

PURPOSE: To evaluate the spectrum of and determine the risk factors for the development of liver toxicity (hepatopathy) after therapy with vincristine, dactinomycin, and cyclophosphamide (VAC) for rhabdomyosarcoma in children and adolescents.

PATIENTS AND METHODS: We prospectively captured all events of hepatopathy occurring on the ongoing Children's Oncology Group intermediate risk protocol, D9803, for children with rhabdomyosarcoma. Patients enrolled onto this trial were randomly assigned to receive either VAC alone or VAC alternating with vincristine, topotecan, and cyclophosphamide. In addition, we reviewed the toxicity database and requested additional information for all patients with elevated bilirubin or transaminase levels. Risk factors were analyzed.

RESULTS: Of 339 patients enrolled through August 2002, 18 developed hepatopathy. All events were captured by mandated toxicity reporting and filing of MedWatch forms, with no additional cases found after the additional search of the database. Four children died after developing this toxicity. All cases occurred after cycles of VAC (n = 16) or vincristine and cyclophosphamide with concomitant abdominal radiotherapy (n = 2). The onset of hepatopathy was 5 to 16 days from the start of a treatment cycle. For the 89 patients under 36 months of age, the risk of hepatopathy was 15%, with two deaths. For the 239 children 3 years of age or older, the risk for hepatopathy was 4%, with two deaths.

CONCLUSION: The greatest risk factor for development of hepatopathy after VAC therapy was age. Dose modifications for younger children receiving VAC therapy are recommended.

Supported by grant Nos. U10 CA098543, U10 CA24507, and CA72989 from the National Cancer Institute, Bethesda, MD.

Presented at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 2, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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]

				S. Laer, J. S. Barrett, and B. Meibohm The In Silico Child: Using Simulation to Guide Pediatric Drug Development and Manage Pediatric Pharmacotherapy J. Clin. Pharmacol., August 1, 2009; 49(8): 889 - 904. [Abstract] [Full Text] [PDF]

				J. S. McCune, D. H. Salinger, P. Vicini, C. Oglesby, D. K. Blough, and J. R. Park Population Pharmacokinetics of Cyclophosphamide and Metabolites in Children With Neuroblastoma: A Report From the Children's Oncology Group J. Clin. Pharmacol., January 1, 2009; 49(1): 88 - 102. [Abstract] [Full Text] [PDF]

				J. T. Mondick, L. Gibiansky, M. R. Gastonguay, J. M. Skolnik, M. Cole, G. J. Veal, A. V. Boddy, P. C. Adamson, and J. S. Barrett Population Pharmacokinetic Investigation of Actinomycin-D in Children and Young Adults J. Clin. Pharmacol., January 1, 2008; 48(1): 35 - 42. [Abstract] [Full Text] [PDF]

				S. Kishi, C. Cheng, D. French, D. Pei, S. Das, E. H. Cook, N. Hijiya, C. Rizzari, G. L. Rosner, T. Frudakis, et al. Ancestry and pharmacogenetics of antileukemic drug toxicity Blood, May 15, 2007; 109(10): 4151 - 4157. [Abstract] [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]

				G. J. Veal, M. Cole, J. Errington, A. Parry, J. Hale, A. D.J. Pearson, K. Howe, J. C. Chisholm, C. Beane, B. Brennan, et al. Pharmacokinetics of Dactinomycin in a Pediatric Patient Population: a United Kingdom Children's Cancer Study Group Study Clin. Cancer Res., August 15, 2005; 11(16): 5893 - 5899. [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]