A phase II study of dose-intense ifosfamide plus epirubicin with hematopoietic growth factors for the treatment of patients with advanced soft tissue sarcomas; a novel sequential schedule.

PURPOSE: The efficacy and feasibility of a novel sequential schedule of high-dose ifosfamide (HD-IFO) and full-dose epirubicin (EPI) with granulocyte colony-stimulating factor (G-CSF) was evaluated in adult patients with soft tissue sarcomas (STS).
METHODS: Since November 1995, 22 chemotherapy-naive patients have been treated. HD-IFO was given as a continuous infusion at a total dose of 14-18 g/m2 per cycle, with mesna, over 6 to 8 days, q 3 weeks, twice. EPI was administered subsequently as an i.v. bolus at a total dose of 120-160 mg/m2, on days 1-2, q 2 weeks, twice. G-CSF was planned for each course of treatment as a daily subcutaneous injection for 7 days, starting 24 h after the end of the treatment. After the first four cycles, patients were evaluated for surgery and patients with locally inoperable or metastatic disease received further chemotherapy up to a maximum of eight cycles.
RESULTS: The response of 19 patients could be assessed. One complete response (CR) and six partial responses (PRs) were achieved for an overall response rate of 37% (95% confidence interval, 15-59%). Noteworthy is that two of the six leiomyosarcoma patients responded to the HD-IFO treatment. The median survival period was 15 months. Most common toxicities included myelosuppression, nausea and vomiting, and stomatitis. Six patients were hospitalized for complicated nadir fever. No severe renal and CNS toxicities were seen. Transient gross hematuria occurred in six patients and affected treatment in only one case. There were no treatment-related deaths.
CONCLUSIONS: By the protraction of continuous infusion of HD-IFO over 6 to 8 days, ifosfamide-induced acute renal toxicity is avoided, while G-CSF support allows the delivery of the planned dose intensity in most of the patients. Although manageable in an oncology setting, the hematologic toxicity of such a regimen remains substantial. Moreover, in terms of efficacy and median survival, this regimen showed no benefits over a conventional-dose anthracycline-ifosfamide schema. Further evaluations of this novel ifosfamide-epirubicin schedule are not warranted, even if the HD-IFO regimen could be taken forward specifically for leiomyosarcomas in a phase II trial.