Pilepich M V, Jones K G, Emami B N, Perez C A, Fields J N, Myerson R J
Radiation Oncology Center, Washington University School of Medicine, St. Louis, MO 63110.
Int J Radiat Oncol Biol Phys. 1989 Jan;16(1):211-3. doi: 10.1016/0360-3016(89)90032-1.
In vitro and animal studies indicate that concomitant administration of Bleomycin and hyperthermia result in a dramatic potentiation of cytotoxic (anti-tumor) activity. This effect takes place at temperatures above 42 degrees C. A Phase I/II pilot study has been conducted to assess the clinical feasibility of concomitant Bleomycin-hyperthermia application. Eligible patients were those with measurable tumors persistent or recurrent following treatment with conventional modalities including full dose radiotherapy. The protocol required placement of at least two interstitial catheters for continuous monitoring of temperature. Skin probes were also used and thermal mapping of all catheters was required. The therapeutic aim was minimal tumor temperature of 43 degrees C +/- .5 degrees C, the maximal normal tissue temperature was not to exceed 45 degrees C. Pretreatment evaluation included pulmonary function studies and arterial blood gases. Bleomycin was administered within 1 hour prior to initiation of hyperthermia at the dose of 15 units/m2. Twelve patients received therapy according to this protocol. Eight presented with carcinomas of the head and neck area, 4 with adenocarcinoma of the breast. Complete response was recorded in 4, partial in 6 patients. Rapid tumor lysis occurred in 2 patients. Reaction of the normal skin and subcutaneous tissues were mild in all cases and ranged from erythema to mild fibrosis. Three patients experienced pulmonary toxicity, only one of which was severe enough to cause cessation of therapy. Early clinical experience with thermochemotherapy using Bleomycin in heavily pretreated patients indicates a promising response rate and acceptable tolerance. Further studies of Bleomycin-hyperthermia alone and in combination with other modalities including radiotherapy appear warranted.
体外和动物研究表明，博来霉素与热疗联合使用可显著增强细胞毒性（抗肿瘤）活性。这种效应发生在42摄氏度以上的温度。已开展一项I/II期初步研究，以评估博来霉素与热疗联合应用的临床可行性。符合条件的患者为经包括全量放疗在内的传统治疗方式治疗后肿瘤持续存在或复发且可测量的患者。该方案要求至少放置两根组织间导管以持续监测温度。还使用了皮肤探头，且要求对所有导管进行热成像。治疗目标是肿瘤最低温度为43摄氏度±0.5摄氏度，正常组织最高温度不超过45摄氏度。治疗前评估包括肺功能研究和动脉血气分析。在开始热疗前1小时内以15单位/平方米的剂量给予博来霉素。12名患者按照该方案接受了治疗。8例为头颈部癌，4例为乳腺癌。4例患者记录为完全缓解，6例部分缓解。2例患者出现快速肿瘤溶解。所有病例中正常皮肤和皮下组织的反应均较轻，从红斑到轻度纤维化不等。3例患者出现肺部毒性，其中只有1例严重到足以导致治疗中断。在经过大量预处理的患者中使用博来霉素进行热化疗的早期临床经验表明，缓解率有望令人满意且耐受性可接受。对单独使用博来霉素热疗以及与包括放疗在内的其他方式联合使用进行进一步研究似乎是有必要的。
