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Effects of Amphotericin B on Adriamycin and Melphalan Cytotoxicity in Human and Murine Ovarian Carcinoma and in L1210 Leukemia

Medicine Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20205

The influence of amphotericin B on the cytotoxicity of Adriamycin and melphalan was examined in three experimental systems of ovarian cancer: (a) a transplantable murine ovarian teratocarcinoma; (b) an established human ovarian cancer cell line; and (c) fresh human epithelial ovarian cancer cells cloned in soft agar. In addition, we studied the effects of melphalan ± amphotericin B on survival of BALB/c x DBA/2 F₁ mice inoculated with either melphalan-sensitive or melphalan-resistant L1210 leukemia.

Simultaneous administration of amphotericin B and Adriamycin in mice with ovarian cancer resulted in long-term survival in 83% of mice compared to 65% of mice treated with Adriamycin alone (p = 0.06). Pretreatment with amphotericin B 24 hr prior to treatment with melphalan produced long-term survival in 44% of mice compared to 7.5% of mice treated with melphalan alone (p < 0.05). Amphotericin B, however, was not able to overcome melphalan resistance in mice inoculated with melphalan-resistant L1210 leukemia cells. Amphotericin B did not potentiate the cytotoxicity of either melphalan or Adriamycin in an established human ovarian cancer cell line.

The effects of amphotericin B together with either melphalan or Adriamycin were also examined in ovarian cancer cells obtained from 15 patients using a soft agar cloning assay. This assay has been demonstrated previously to be capable of identifying anticancer agents which have a high probability of producing responses in individual patients. However, even under experimental conditions selected to optimize the likelihood of observing in vitro amphotericin B potentiation of cytotoxicity, we could not demonstrate a reduction in tumor colony formation to the degree required to predict for clinical utility in cells obtained from relapsed patients. These results indicate that, while amphotericin B can potentiate the effects of Adriamycin and melphalan in certain murine tumors, it is not likely to overcome Adriamycin or melphalan resistance in most ovarian cancer patients who have relapsed following treatment with these drugs.

¹ To whom requests for reprints should be addressed, at Medicine Branch, National Cancer Institute, Bldg. 10, Room 12N266, 9000 Rockville Pike, Bethesda, Md. 20205.

Received 6/21/82. Accepted 11/16/82.