Interaction of bleomycin and hyperthermia--results of a clinical pilot study.

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.