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 with 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 ≥ 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 μg/ml to 0.78 μg/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 ≥ 50% colony inhibition when exposed to 2-fluoro-Ara-AMP or cisplatin than did those from previously treated patients. Our data suggest that 2-fluoro-Ara AMP has in vitro activity against gynecologic tumors (predominantly ovarian). Tumors from untreated patients were more sensitive than tumors from treated patients. At all concentrations of 2-fluoro-Ara AMP tested, bone marrow cells were more sensitive than the tumor cells suggesting a concerning notion that the clinical efficacy of this agent could be compromised by the myelosuppressive properties of this agent.