AMD473 (ZD0473) exhibits marked in vitro anticancer activity in human tumor specimens taken directly from patients

Leticia Medina-Gundrum, Cesario Cerna, Lionel R. Gomez, Michael Yochmowitz, Steven Weitman

Resultado de la investigación: Articlerevisión exhaustiva

7 Citas (Scopus)

Resumen

AMD473 (ZD0473; cis-amminedichloro[2-methylpyridine]-platinum [II]) is a new generation anticancer agent that, in preclinical studies, shows evidence of an extended spectrum of antitumor activity and overcomes platinum resistance mechanisms. Here we evaluate the activity of AMD473 (ZD0473) in a panel of 120 human tumor specimens using a soft agar cloning assay (human tumor colony-forming assay). When tumor cells were treated with 1.0, 4.0 or 16.0 μg/ml AMD473 (ZD0473) for 2h, in vitro responses were observed in 18% (9/51), 33% (17/51) and 44% (19/43) of assessable specimens. Treatment of tumor cells with the same concentrations of AMD473 (ZD0473) for 24 h resulted in responses of 33% (16/48), 63% (30/48) and 85% (35/41). AMD473 (ZD0473) (16 μg/ml; 24 h) demonstrated activity towards 100% of the non-small cell lung (5/5) and ovarian (8/8) cancer specimens and 73% (8/11) of the breast cancer specimens treated. Low levels of cross-resistance to cisplafin cyclophosphamide, 5-flurouracil, etoposide and gemcitabine were observed. There was a positive relationship between AMD473 (ZD0473) concentration and effect, and a significant difference between response to 2- versus 24-h exposure to 4 or 16 μg/ml (p=0.003 and p=0.001, respectively). These responses demonstrate efficacy at pharmacologically relevant concentrations, suggesting AMD473 (ZD0473) deserves further evaluation.

Idioma originalEnglish (US)
Páginas (desde-hasta)275-280
Número de páginas6
PublicaciónAnti-cancer drugs
Volumen14
N.º4
DOI
EstadoPublished - abr 1 2003

ASJC Scopus subject areas

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

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