Randomized Phase III Study Comparing Conventional-Dose Doxorubicin Plus Ifosfamide Versus High-Dose Doxorubicin Plus Ifosfamide Plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Soft Tissue Sarcomas: A Trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group

作者：Axel Le Cesne, Ian Robert Judson, D. Crowther, Sjoerd Rodenhuis, H. J. E. Keizer, Q. van Hoesel, Jean‐Yves Blay, Jürgen Frisch, Martine Van Glabbeke, C. Hermans, Allan van Oosterom, Thomas Tursz, Jaap Verweij · 发表于：Journal of Clinical Oncology · 年份：2000 · DOI：10.1200/jco.2000.18.14.2676 · 被引用次数：259 · 研究领域：Sarcoma Diagnosis and Treatment、Cancer Research and Treatments、Gastrointestinal Tumor Research and Treatment

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m(2) on day 1) and ifosfamide (5 g/m(2) on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m(2) on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 microgram/m(2) on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P =.65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P =.03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified a...