Based on a phase I study in 1986, 22 patients have been entered in a phase II study of high-dose human tumor necrosis factor (rH-TNF) since May 1987. Of these patients, 18 are evaluable at present, 2 are still under investigation, and 2 have dropped out. All had advanced stages of cancer (9 soft-tissue sarcomas, 3 melanomas, 5 hypernephromas) and inclusion in the study was ethically acceptable (informed consent). The daily dose of rH-TNF was 15 x 10(5) units/m2, escalated to 21 x 10(5) units/m2 (683-956 micrograms/m2 every week; range 1-6 cycles). Additional prophylactic ketoprofen administration was carried out. Of the 18 evaluable patients, 4 responded with no change (2/4, clinical improvement) and 14 showed progressive disease. The main toxicities observed were hypotension (decrease in systolic blood pressure, 21-60 Torr), leukocytosis, increases in ALAT/ASAT (WHO grade 0-4), fever (WHO grade 1-2), chills (mild to moderate), neurotoxicity (WHO grade 0-2), and nausea/vomiting (WHO grade 0-3).

Fourteen patients with metastatic breast cancer previously treated with one chemotherapy regimen received Pirarubicin at a dose of 70 mg/m² at 3-week intervals. In 7 patients the dose had to be reduced, in 1 patient to 40 mg/m² and in 6 patients to 50–60 mg/m². There were 1 complete and 2 partial remissions. These objective responses were observed in soft tissue, lung and pleural areas and lasted 1+; 4+ and 5+ months. Grade 3 and 4 leukopenia was found in 42%, grade 3 thrombocytopenia in 2%, grade 3 nausea/vomiting in 29% of the cycles. Grade 1 and 2 alopecia occurred in 64% of the patients, the remaining 36% of the patients did not suffer from any alopecia. No cardiotoxic side effects were observed in 13 patients. In 1 patient with severe coronary heart disease extrasystoles and reduction in left ventricular ejection fraction occurred. Pirarubicin has antitumor activity in previously treated metastatic breast cancer patients.

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