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

两项早期研究设计了一项II期试验，采用41.8摄氏度（x 60分钟）体外全身热疗（WBH）联合ICE，即异磷酰胺（5 g/m2）、卡铂（300 mg/m2）和依托泊苷（WBH），以及WBH后第2天和第3天（100 mg/m2）治疗难治性肉瘤成人患者。12名患者参加了这项试验；所有这些都是可评估的。8例患者既往有与疾病进展相关的化疗史。在WBH/ICE之后，观察到7例部分缓解（58%）；3例患者病情稳定；上述10名患者每人接受4个疗程的治疗。2例患者病情进展。观察到的世卫组织分级（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(1;6)。其他毒性（1级和2级）包括：便秘、腹泻、室性心律失常、压疮和口周单纯疱疹。基于对毒性数据的分析，采用了另一种WBH技术，即辐射热，以降低发病率。威斯康星大学开发的这项技术消除了上述毒性（与体外白血病有关）。迄今为止（1996年4月），在吕贝克大学正在进行的辐射热白头病试验中，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，这项试验现在变成了一项多机构试验。该试验的结果将为多机构III期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.