Babović N, Jelić S, Milanović N, Matković S
Institute of Oncology and Radiology of Serbia, Belgrade, Yugoslavia.
Tumori. 1998 Nov-Dec;84(6):677-80. doi: 10.1177/030089169808400613.
Second-line chemotherapy regimens for advanced soft tissue sarcomas after treatment failure or tumor relapse following anthracyclines are still investigational. The aim of the present study was to assess the activity of ifosfamide with a new schedule for patients with advanced soft tissue sarcoma failing to achieve remission or relapsing following anthracycline-containing regimens; it was attempted to individualize dosages and prevent excessive toxicity.
A second-line chemotherapy regimen of ifosfamide 1 g/m2 daily, 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/m2 or zorubicin 600 mg/m2 per cycle). The cycles were repeated every four weeks.
The median number of cycles applied was three (range, 1-15). The ifosfamide dosage reached was 4-13 g/m2 per cycle, median 5 g/m2. A complete 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 progressive disease. No difference in response and stable disease rates was observed between responders and non-responders to first-line chemotherapy. No difference in the ifosfamide dose reached was noted between patients receiving second-line chemotherapy directly following first-line therapy and those with a time interval between first- and second-line chemotherapy. The granulocytopenia grade III nadir lasted for a median of one day (range, 1-3) and other toxicities including hematological toxicity were mild and infrequent.
In view of the swift regeneration from grade III granulocytopenia, 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.
蒽环类药物治疗失败或肿瘤复发后晚期软组织肉瘤的二线化疗方案仍在研究中。本研究的目的是评估异环磷酰胺新方案对含蒽环类方案治疗后未缓解或复发的晚期软组织肉瘤患者的活性；试图实现剂量个体化并预防过度毒性。
对21例晚期软组织肉瘤患者给予异环磷酰胺每日1 g/m²的二线化疗方案，出现III级粒细胞减少时停药直至下一周期。所有患者一线高剂量蒽环类方案（表柔比星每周期180 mg/m²或柔红霉素每周期600 mg/m²）治疗后未缓解或复发。每四周重复一个周期。
应用周期的中位数为3个（范围1 - 15）。每周期异环磷酰胺剂量达4 - 13 g/m²，中位数为5 g/m²。21例患者中1例（5%）获得完全缓解，未观察到部分缓解，4例（20%）疾病稳定，16例（75%）疾病进展。一线化疗有反应者与无反应者之间在反应率和疾病稳定率上无差异。一线治疗后直接接受二线化疗的患者与一线和二线化疗之间有时间间隔的患者在达到的异环磷酰胺剂量上无差异。III级粒细胞减少最低点持续时间的中位数为1天（范围1 - 3），包括血液学毒性在内的其他毒性轻微且不常见。
鉴于III级粒细胞减少迅速恢复，以IV级粒细胞减少作为异环磷酰胺剂量递增的限制因素继续本研究似乎可行，有望在不过度毒性的情况下获得更好疗效。
