Activity of 2-fluoro-Ara AMP against gynecologic tumors in the soft agar assay.
To characterize in vitro activity of 2-fluoro-Ara AMP and its relation to the activities of cisplatin and doxorubicin, 28 specimens from patients wit gynecologic tumors (predominantly ovarian) were tested in a soft agar assay. Twenty-six of 28 (93%) grew when the medium was supplemented with four hormones (epidermal growth factor, hydrocortisone, estradiol-17, and insulin). Normal bone marrow cells were utilized as a biologic control to define in vitro concentrations of the three drugs. Tumors were exposed continuously to three different concentrations of each drug. 2-fluoro-Ara AMP was tested against 26 tumors, cisplatin against 24, and doxorubicin against 14. In vitro sensitivity was defined as greater than or equal to 50% colony inhibition at a drug concentration within the bone marrow inhibitory range. Seven of 26 (27%) tumor specimens were sensitive to 2-fluoro-Ara AMP. Among these, four tumors were derived from previously treated patients. However, in the 2-fluoro-Ara AMP concentration range (0.26 micrograms/ml to 0.78 micrograms/ml) tested, five of eight (62.5%) tumors from untreated patients achieved IC50 compared to only seven of 18 (39%) tumors from treated patients. Five of six (83%) specimens demonstrated cross-sensitivity between cisplatin and 2-fluoro-Ara AMP. Seventeen of 18 (94%) specimens demonstrated cross-resistance between cisplatin and 2-fluoro-Ara AMP, and 13 of 13 (100%) specimens demonstrated cross-resistance between 2-fluoro-Ara AMP and doxorubicin. A higher proportion of tumors from previously untreated patients achieved greater than or equal to 50% colony inhibition when exposed to 2-fluoro-Ara-AMP or cisplatin than did those from previously treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
D000362:Agar; D001088:Arabinonucleotides / Q000627:therapeutic use*; D001854:Bone Marrow Cells; D002945:Cisplatin; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D003470:Culture Media; D046508:Culture Techniques; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives / Q000627:therapeutic use*
D001088:Arabinonucleotides; D003470:Culture Media; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; D004317:Doxorubicin; D000362:Agar; D002945:Cisplatin