Thirty patients with local relapses after radical mastectomy and radiotherapy and undergoing infusion of liposomal doxorubicin (40 mg/m(2) monthly for 6 months) were randomized to receive re-irradiation. Radiotherapy was with either 17 fractions of 1.8 Gy, 5 days a week (N=15, group A) or 4 Gy plus two fractions of 3 Gy the 1st week and six fractions of 3 Gy given every second day (N=15, group B). Eight patients from group A (53.3%) and nine patients (60%) from group B demonstrating a clinically complete response (P=0.9). Grade I/II acute skin toxicity was monitored in 26.6% of patients in group A versus 73.3% in group B. The radiation schedule of group A seems superior for grade I/II acute (P=0.027) and late (P=0.015) skin toxicity. The linear quadratic model enabled the prediction of tumor response as well as normal skin reactions.