4'-Epi-doxorubicin (4'-epi-DX) is a new doxorubicin derivative that in phase II human studies has been demonstrated to be less toxic than doxorubicin. Sixty-four patients with advanced solid tumors were treated with the drug combination of 4'-epi-DX and cis-dichlorodiammineplatinum (CDDP) at the doses of 40-60 and 50 mg/m2, respectively, every 21-28 days. Out of 52 evaluable patients, complete remission (CR) was recorded in 5, partial remission (PR) in 12, minor remission (MR) in 7, no change (NC) in 16 and progression (P) in 12. The median duration of remission in patients who achieved a CR and PR was 9+ months. In particular, out of 19 patients with ovarian cancer, 2 CR (second look) and 7 PR have been documented. One CR and 3 PR also have been observed in 21 patients with lung carcinoma. Complete and partial responses also have been documented in breast cancer (1 CR/1), in bladder carcinoma (1 CR/2), in renal cancer (1 PR/5) and in testicular cancer (1 PR/1). Hematologic toxicity was generally mild to moderate (leukopenia less than or equal to 1500 cells/mm3 in 3% of the patients; thrombocytopenia less than or equal to 120,000 cells/mm3 in 2% of the patients). Vomiting was present in almost all patients while alopecia has been recorded in 63% of the patients. No case of cardiac toxicity had been observed up to now (median cumulative dose of 4'-epi-DX:240 mg/m2, range 40-650 mg/m2). The combination of 4'-epi-DX with CDDP appears to be an active and well-tolerated regimen in ovarian cancer and lung cancer.

High dose MAP (medroxyprogesterone acetate) and TAM (tamoxifen) were administered orally to 31 postmenopausal patients with advanced breast cancer. CR (complete remission) was achieved in 1 (3%) and PR (partial remission) in 11 (32%) patients for a median duration of 12 months. The treatment was well tolerated and in no instance was interrupted because of toxicity. This study does not support the hypothesis that the combination of MAP and TAM gives better results than the single agents.

Thirty-two patients with advanced ovarian cancer were treated with a combination of 4'-epi-doxorubicin, a new analog of doxorubicin, and cisplatin at a dose of 60 and 50 mg/m2, respectively, every 28 days. Twelve patients had previously received chemotherapy and/or radiotherapy. Of 29 evaluable patients, six (21%) achieved complete remission for a median duration of 19+ months, and 13 (45%) achieved partial remission for a median duration of 8 months. All complete remissions were confirmed by a "second-look" procedure. Main side effects included vomiting in all patients, moderate myelosuppression (67%), and alopecia (65%). No case of congestive heart failure was observed. 4'-Epi-doxorubicin plus cisplatin is an effective and relatively well-tolerated regimen in the treatment of advanced ovarian cancer.