A phase I/II study of combined cisplatin and hyperthermia treatment for refractory malignancy

Abstract

Research in animal and human cell cultures has shown that some chemotherapeutic agents, cisplatin in particular, have cytotoxicity that is significantly potentiated at elevated temperatures. Concurrent administration of systemic cisplatin and local hyperthermia in human patients has not been previously reported. A phase I/II study was undertaken to assess the systemic and local toxicities and activity of concurrently administered local hyperthermia and systemic cisplatin in human tumours. Nine patients with histologically proven malignant tumours have been treated from March 1985 to July 1987. Their histologies were: breast, four; SCC of head and neck, two; SCC of skin, one; malignant melanoma, one; synovial cell sarcoma, one. Once-weekly hyperthermia was administered for 60 min by external microwave devices in an attempt to achieve minimum intratumoral temperatures of 42°C. Plastic catheters were placed intratumorally under CT guidance for thermometry purposes. Cisplatin 40–60 mg/m² was given over 60 min when steady-state heating was achieved. A total of 44 treatments are available for analysis. All nine patients had minimum Lntratumoral temperatures below the desired goal of 42°C, and only two patients achieved average intratumoral temperatures of 42°C or greater. Two of the responding patients sustained significant thermal injury consisting of blistering and necrosis. Three patients required transfusion and delay of weekly treatment because of anaemia and leukopenia. Four patients had partial response (PR) and one patient had minor response (MR) within the heated treatment volume. Three of these five patients experienced significant subjective palliation. This combination of treatment modalities can be delivered safely. The low and non-uniform intratumoral temperatures achievable with current hyperthermia equipment limits the efficacy of this regimen. Since there is some evidence of activity in these refractory malignancies, further studies designed to optimize the synergistic cytotoxicity of local hyperthermia and cisplatin are warranted.