Evaluation of 3-(p-fluorophenyl)-l-alanyl-3-[m-bis(2-chloroethyl)aminophenyl]-l-alanyl-l-methionine ethyl ester HCl (PTT.119) against xenografts of human rhabdomyosarcoma

Peter J. Houghton, Ruby Tharp, Janet A. Houghton, J. F. Holland, J. George Bekesi

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1 Scopus citations

Abstract

PTT.119 [p-F-phe-m-bis(2-chloroethyl)amino-l-phe-met ethoxy HCl], a synthetic tripeptide mustard, was evaluated for therapeutic efficacy against a spectrum of childhood rhabdomyosarcomas (RMS) maintained as xenografts in immune-deprived mice. These xenografts were established from previously untreated tumors, and sublines were selected in mice for resistance to l-phenylalanine mustard (L-PAM). PTT.119 caused regression of four of six RMS lines established from untreated tumors, and demonstrated activity similar to that of L-PAM in this model. Against tumors Rh18/L-PAM and Rh28/L-PAM, selected in situ for L-PAM resistance, PTT.119 had no significant activity. Rh28/L-PAM was cross-resistant also to oxazophosphorine mustards (ifosfamide, cyclophosphamide), and both tumors were cross-resistant to adriamycin and vincristine. PTT.119 caused hematologic toxicity similar to thet of L-PAM, characterized by a marked decrease in white blood cells and thrombocytopenia.

Original languageEnglish (US)
Pages (from-to)201-204
Number of pages4
JournalCancer chemotherapy and pharmacology
Volume22
Issue number3
DOIs
StatePublished - Sep 1988
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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