Pilot study of daily ifosfamide 1 g/m(2) until grade III granulocytopenia as second-line chemotherapy for anthracycline-pretreated advanced soft tissue sarcoma

Background and aims: Second-line chemotherapy regimens for advanced soft ti ssue sarcomas after treatment failure or tumor relapse following anthracycl ines are still investigational. The aim of the present study was to assess the activity of ifosfamide with a new schedule for patients with advanced s oft tissue sarcoma failing to achieve remission or relapsing following anth racycline-containing regimens; it was attempted to individualize dosages an d prevent excessive toxicity, Study design: A second-line chemotherapy regimen of ifosfamide 1 g/m(2) dai ly, with drug withdrawal until the next cycle upon appearance of grade III granulocytopenia, was administered to 21 patients with advanced soft tissue sarcoma. All patients failed to achieve remission or relapsed following a first-line high-dose anthracycline regimen (epirubicin 180 mg/m(2) or zorub icin 600 mg/m(2) per cycle). The cycles were repeated every four weeks. Results: The median number of cycles applied was three (range, 1-15). The i fosfamide dosage reached was 4-13 g/m(2) per cycle, median 5 g/m(2). A comp lete response was achieved in 1/21 patient (5%), no partial responses were observed, 4/21 patients (20%) had stable disease, and 16/21 (75%) had progr essive disease. No difference in response and stable disease rates was obse rved between responders and non-responders to first-line chemotherapy. No d ifference in the ifosfamide dose reached was noted between patients receivi ng second-line chemotherapy directly following first-line therapy and those with a time interval between first- and second-line chemotherapy. The gran ulocytopenia grade III nadir lasted for a median of one day (range, 1-3) an d other toxicities including hematological toxicity were mild and infrequen t. Conclusions: In view of the swift regeneration from grade III granulocytope nia, continuation of the study with granulocytopenia grade IV as a limiting factor for ifosfamide dose escalation seems feasible, with the prospect of better efficacy without excessive toxicity.