Antitumor activity of new anthracycline analogues in combination with interferon alfa

Combinations of recombinant interferon alfa2 (IFN-alpha 2) with doxorubicin, 4'-epidoxorubicin, 4'-deoxydoxorubicin, or 4-demethoxydaunorubicin were tested for antiproliferative activity against a panel of human tumor cell lines in a human tumor clonogenic assay. The histologies of the cell lines were ovary, cervix, breast, and melanoma. Each of the cytotoxic compounds showed dose-dependent antiproliferative effects against each of the cell lines, and the results indicated that doxorubicin derivatives were consistently more potent than the parent drug. In all instances, 4-demethoxydaunorubicin was the most potent derivative, requiring 2-20 times less drug to inhibit 70% of tumor colony formation. Combinations of IFN-alpha 2, with doxorubicin or its derivatives may show additive or synergistic antiproliferative activity against certain tumor cell lines. The ovarian carcinoma cell line, BG-1, responded synergistically to each of the four compounds in combination with IFN-alpha 2. The cervical carcinoma cell line, CaSki, and the breast carcinoma line, MCF-7, responded to the combinations in a manner best described as additive. In the melanoma line, SK-Mel-28, the drugs were found to be subadditive or even antagonistic. While the potency of the anthracycline derivatives ranked consistently across the different cell lines, the synergistic interaction with IFN-alpha 2 is a cell line-specific phenomenon unrelated to sensitivity to either anthracyclines or interferon.