Dinaline: a new oral drug against leukemia? Preclinical studies in a relevant rat model for human acute myelocytic leukemia (BNML).
The efficacy and toxicity of Dinaline (GOE 1734; PD 104 208; NSC 328786; 4-amino-N-(2'-aminophenyl)benzamide) was evaluated in the Brown Norway acute myelocytic leukemia, which is generally accepted as a relevant preclinical model for human acute myelocytic leukemia. Upon repeated daily oral administration at least an 8 log leukemic cell kill was achieved with only less than a 1 log kill for normal pluripotent hemopoietic stem cells. Daily split-dose treatment even proved to be more effective and resulted in 40-50% cures. However, toxicity was also more pronounced in particular in regard to the gastrointestinal tract. So far, the mode of action of Dinaline is unknown, but its striking therapeutic index warrants further clinical investigation.
Hagenbeek
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Radiobiological Institute TNO, Rijswijk, The Netherlands.
Weiershausen
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Martens
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AC
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010655:Phenylenediamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN
D000970:Antineoplastic Agents; D010655:Phenylenediamines; C045838:dinaline