PHASE II WBH AND IFOSFAMIDE/CARBOPLATIN/ETOPOSIDE THERAPY IN SARCOMA

早些时候的两项研究导致了一项II期试验的设计，即41.8摄氏度(x 60分钟)体外全身热疗(WBH)联合ICE，即异环磷酰胺(5g/m2)，卡铂(300 mg/m2)，依托泊苷与WBH一起使用，以及WBH后第2天和第3天(100 mg/m2)治疗成人难治性肉瘤。12名患者参加了这项试验；所有患者都是可评估的。8名患者有与疾病进展相关的既往化疗病史。在WBH/ICE后，观察到7例部分缓解(58%)；3名患者病情稳定；上述10名患者每人接受了4个周期的治疗。两名患者表现为进展性疾病。观察到的WHO分级(3；或4)毒性事件包括：红细胞(2；2)；白细胞(5；7)；血小板(1；6)；肾脏(1；6)。其他毒性反应(1级和2级)包括：腹痛、腹泻、室性心律失常、压疮和口腔周围单纯疱疹。基于对毒性数据的分析，采用了另一种WBH技术，即辐射热，以减少发病率。威斯康星大学开发的这项技术已经消除了上述毒性(与体外WBH有关)。到目前为止(1996年4月)，在吕贝克大学正在进行的辐射热疗WBH试验中，12名患者中有7名有反应。随着威斯康星大学和埃森大学的加入，这项试验现在正在成为一项多机构试验。这项试验的结果应为多机构第三阶段研究提供坚实的基础。

Two earlier studies resulted in the design of a phase II trial of 41.8-degree-celsius (x 60 min) extracorporeal whole body hyperthermia (WBH) with ICE, i.e., ifosfamide (5 g/m2), carboplatin (300 mg/m2), and etoposide given with WBH, as well as day 2 and 3 post WBH (100 mg/m2) for adult patients with refractory sarcoma. Twelve patients entered this trial; all were evaluable. Eight patients had a history of prior chemotherapy associated with disease progression. Following WBH/ICE, seven partial remissions were observed (58 percent); three patients experienced disease stabilization; the aforementioned ten patients each received four cycles of therapy. Two patients exhibited progressive disease. Episodes of WHO-graded (3; or 4) toxicity observed included: red blood cell (2;2); white blood cell (5;7); platelet (1;6); renal (1;6). Other toxicities (grade 1 and 2) included: anasarca, diarrhea, ventricular arrhythmias, pressure sores, and perioral herpes simplex. Based on an analysis of the toxicity data, an alternative WBH technology, i.e., radiant heat, was adopted to reduce morbidity. This technology developed at the University of Wisconsin, has eliminated the aforementioned toxicities (associated with extracorporeal WBH). To date (April 1996), seven of twelve patients have had responses in an ongoing radiant heat WBH trial at the University of Lubeck. This trial is now becoming a multi-institutional trial with the addition of the University of Wisconsin and the University of Essen. The results of this trial should provide a solid foundation for a multi-institutional phase III study.