Sixty patients with stage III-B and IV soft tissue sarcomas were randomized to receive either ifosfamide 5g/m(2)xdx1 and doxorubicin 60mg/m(2)xdx1 given every 3 weeks (arm A) or ifosfamide 1.8g/m(2)xdx5 and doxorubicin 60mg/m(2)xdx1 given every 4 weeks (arm B). Recombinant human granulocyte colony-stimulating factor (r-met Hu G-CSF: 250 mu g/m(2)xd) was applied with a prophylactic intent to patients in arm A only. The response rate was higher in arm A patients (56% versus 33%, p=0.03). In stage III patients, the complete response rate was significantly higher (53% versus, 13.3%, p=0.01) and the duration of response was significantly longer in arm A (20+/-8.2 months versus, 13.4+/-7 months, p=0.05). Chemotherapy related myelotoxicity and mucositis were also less frequent in this arm as a result of propylactic r-met Hu G-CSF administration (p=0.04, p=0.003).