The efficacy and toxicity of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP) were assessed in the treatment of patients with advanced breast cancer by the Japan THP Study Group. Mean plasma levels of THP after single-dose administration revealed triexponential decay characterized by an initial half-life of 0.89 h. A higher concentration of THP was obtained in the metastatic lymph nodes than in the breast cancer tissue at 4 h after administration (4.01 vs. 1.17 micrograms/g). Whereas 1 complete (CR) and 12 partial response (PR) were observed in 56 evaluable patients after administration of THP alone (23.2%), 1 CR and 12 PR were observed in 37 evaluable patients who had combination therapy including THP (35.1%). Multivariate analysis of prognostic factor revealed that the site of metastases had the most valuable prognostic significance; second was irradiation in the previous treatment, and third was the disease-free interval. Life-table analysis adjusted with the Cox proportional hazard model revealed a similar survival curve of patients receiving THP-cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) to that of those receiving CAF only in spite of the low incidence of toxicity in the THP therapy.