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.

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 that of L-PAM, characterized by a marked decrease in white blood cells and thrombocytopenia.

• Authors: P J Houghton, R Tharp, J A Houghton, J F Holland, J G Bekesi
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 22 Issue 3 Pg. 201-4 ( 1988) ISSN: 0344-5704 [Print] Germany
• PMID: 3409455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Nitrogen Mustard Compounds
• ambamustine
• Melphalan

Topics

• Animals
• Antineoplastic Agents (therapeutic use, toxicity)
• Cell Line
• Drug Resistance
• Drug Screening Assays, Antitumor
• Female
• Humans
• Immunosuppression Therapy
• Leukocyte Count (drug effects)
• Melphalan (therapeutic use, toxicity)
• Mice
• Mice, Inbred CBA
• Neoplasm Transplantation
• Nitrogen Mustard Compounds (therapeutic use, toxicity)
• Platelet Count (drug effects)
• Rhabdomyosarcoma (drug therapy)