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.
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.
Houghton
P J
PJ
Laboratories for Developmental Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Tharp
R
R
Houghton
J A
JA
Holland
J F
JF
Bekesi
J G
JG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007958:Leukocyte Count / Q000187:drug effects; D008558:Melphalan / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use* / Q000633:toxicity; D010976:Platelet Count / Q000187:drug effects; D012208:Rhabdomyosarcoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C038259:ambamustine; D008558:Melphalan