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Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development.

Publication ,  Journal Article
Horowitz, ME; Etcubanas, E; Christensen, ML; Houghton, JA; George, SL; Green, AA; Houghton, PJ
Published in: J Clin Oncol
February 1988

We describe events that led to successful testing of melphalan, one of the nitrogen mustard compounds, in children with newly diagnosed, poor-risk rhabdomyosarcoma (RMS). Preclinical studies with xenografts of human RMS, growing in the flanks of immune-deprived mice, had indicated superior oncolytic activity by melphalan compared with other agents commonly used to treat this tumor. However, in a conventional phase II trial, melphalan failed to produce partial responses in 12 of 13 heavily pretreated patients with recurrent tumors. Subsequent comparison of the drug's pharmacokinetics in mice and patients indicated that its poor clinical performance was not the result of interspecies differences in drug disposition. Therefore, we elected to retest melphalan in untreated patients, before they were enrolled in a phase III study. Of 13 children who received the drug for 6 weeks, ten had partial responses, confirming the significant antitumor activity seen in the xenograft system. These findings illustrate the inherent limitations of phase II drug trials in previously treated patients and suggest a useful paradigm for the development of antineoplastic drugs.

Duke Scholars

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

February 1988

Volume

6

Issue

2

Start / End Page

308 / 314

Location

United States

Related Subject Headings

  • Rhabdomyosarcoma
  • Oncology & Carcinogenesis
  • Models, Biological
  • Metabolic Clearance Rate
  • Melphalan
  • Male
  • Humans
  • Female
  • Drug Resistance
  • Drug Evaluation
 

Citation

APA
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ICMJE
MLA
NLM
Horowitz, M. E., Etcubanas, E., Christensen, M. L., Houghton, J. A., George, S. L., Green, A. A., & Houghton, P. J. (1988). Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development. J Clin Oncol, 6(2), 308–314. https://doi.org/10.1200/JCO.1988.6.2.308
Horowitz, M. E., E. Etcubanas, M. L. Christensen, J. A. Houghton, S. L. George, A. A. Green, and P. J. Houghton. “Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development.J Clin Oncol 6, no. 2 (February 1988): 308–14. https://doi.org/10.1200/JCO.1988.6.2.308.
Horowitz ME, Etcubanas E, Christensen ML, Houghton JA, George SL, Green AA, et al. Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development. J Clin Oncol. 1988 Feb;6(2):308–14.
Horowitz, M. E., et al. “Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development.J Clin Oncol, vol. 6, no. 2, Feb. 1988, pp. 308–14. Pubmed, doi:10.1200/JCO.1988.6.2.308.
Horowitz ME, Etcubanas E, Christensen ML, Houghton JA, George SL, Green AA, Houghton PJ. Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development. J Clin Oncol. 1988 Feb;6(2):308–314.

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

February 1988

Volume

6

Issue

2

Start / End Page

308 / 314

Location

United States

Related Subject Headings

  • Rhabdomyosarcoma
  • Oncology & Carcinogenesis
  • Models, Biological
  • Metabolic Clearance Rate
  • Melphalan
  • Male
  • Humans
  • Female
  • Drug Resistance
  • Drug Evaluation