Jäger E, Klein O, Wächter B, Bernhard H, Dippold W, Meyer zum Büschenfelde K H, Knuth A
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Oncology. 1996 Jan-Feb;53(1):58-63. doi: 10.1159/000227536.
Treatment results of advanced soft tissue sarcomas are still suboptimal. To evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5-fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study was initiated in patients with advanced soft tissue sarcomas of different histological subtypes. Fifty-six previously untreated patients with advanced soft tissue sarcomas of different histological subtypes (24 females, 31 males, median age 51.3 years, median Karnofsky performance status 80%) were included in this study. Treatment consisted of ADM 50 mg/m2 i.v. on day 1, IFO 4,000 mg/m2 i.v. on day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO administration, FU 500 mg/m2 i.v. as 24-hour infusion on days 1 + 2, DDP 100 mg/m2 i.v. on day 2. This regimen was repeated every 4 weeks for at least 2 cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56 patients. One toxic death due to severe neutropenia and fungal pneumonia occurred. Granulocyte colony-stimulating factor was administered in 8/35 neutropenic patients. Time to recovery was significantly reduced and no infectious complication was observed. WHO grade III/IV toxic diarrhea was observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with ondansetron alone. The overall response rate was 30.3%. The median duration of response (complete/partial response, CR/PR) was 18.1 months, the median progression-free interval was 4.5 months. The median survival time of all patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor-related pain was effectively reduced in 15/31 patients under treatment. FADIP produces comparable response rates to other standard treatment regimens in soft tissue sarcomas. Prolonged duration of response and median survival may be due to the use of continuous infusion of FU as a synergistic factor to alkylating agents. Granulocyte colony-stimulating factor is effective in reducing the otherwise observed high rate of WHO grade III/IV hematological toxicity with severe neutropenia.
晚期软组织肉瘤的治疗效果仍不尽人意。为评估阿霉素（ADM）、异环磷酰胺（IFO）、顺铂（DDP）联合持续输注5-氟尿嘧啶（FU）作为烷化剂协同因子的联合疗法（FADIP）的临床疗效，针对不同组织学亚型的晚期软组织肉瘤患者开展了一项II期研究。本研究纳入了56例既往未接受过治疗、不同组织学亚型的晚期软组织肉瘤患者（24例女性，31例男性，中位年龄51.3岁，中位卡诺夫斯基功能状态为80%）。治疗方案为：第1天静脉注射ADM 50 mg/m²，第1天静脉注射IFO 4000 mg/m²，从IFO给药开始，第1天静脉注射美司钠800 mg/m²，每8小时1次，共3次；第1天和第2天静脉持续输注FU 500 mg/m²；第2天静脉注射DDP 100 mg/m²。该方案每4周重复一次，至少进行2个周期。56例患者中有35例出现了世界卫生组织（WHO）III/IV级主要血液学毒性。发生了1例因严重中性粒细胞减少和真菌性肺炎导致的毒性死亡。35例中性粒细胞减少患者中有8例接受了粒细胞集落刺激因子治疗。恢复时间显著缩短，未观察到感染性并发症。8例患者出现WHO III/IV级毒性腹泻，需要静脉补液。11例患者出现WHO III/IV级恶心，其中9例仅接受昂丹司琼对症治疗后有反应。总缓解率为30.3%。缓解持续时间（完全缓解/部分缓解，CR/PR）的中位数为18.1个月，无进展生存期的中位数为4.5个月。所有患者的中位生存时间为11.8个月，缓解患者（CR/PR）的中位生存时间为18.1个月。15/31例接受治疗的患者肿瘤相关疼痛得到有效减轻。FADIP在软组织肉瘤中的缓解率与其他标准治疗方案相当。缓解持续时间和中位生存期的延长可能归因于将FU持续输注作为烷化剂的协同因子使用。粒细胞集落刺激因子可有效降低原本观察到的伴有严重中性粒细胞减少的WHO III/IV级血液学毒性的高发生率。
