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 degrees 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 intratumoral temperatures below the desired goal of 42 degrees C, and only two patients achieved average intratumoral temperatures of 42 degrees 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment outcome analysis of chemotherapy combined with modulated electro-hyperthermia compared with chemotherapy alone for recurrent cervical cancer, following irradiation

“…Thus, the application of deep local hyperthermia along with the systemic administration of cisplatin appears to be an attractive option in patients with recurrent pelvic cervical cancer. Once initial feasibility data regarding the clinical use of cisplatin and local hyperthermia combination treatment were reported (29), Rietbroek et al (7) published a phase II study of combined weekly locoregional hyperthermia and systemic cisplatin administration in patients with previously irradiated recurrent cervical carcinoma (30). Using a regimen of 50 mg of cisplatin per week with a one-week interruption following four cycles for a total of 12 cycles, corresponding to a projected dose intensity of 40 mg per week, these authors observed an overall response in 12/23 patients (52%; 95% confidence interval, 31–73%) (7).…”

Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix

“…The median survival was 9 / months identified SCC-Ag responders had developed clinical / 7b4e$$0921 02-11-97 08:46:26 canxa W: Cancer PD at last follow-up; in all four patients SCC-Ag in-use cisplatin and HT in a dose of 50 mg/m 2 /week for a period of 6 weeks. [26][27][28][29][30] Because the authors believed creased significantly. that 6 weekly cycles might not be sufficient for induction of worthwhile responses, they chose to treat pa-…”

Cisplatin and Hyperthermia Treatment of A C3H Mammary Carcinoma in Vivo: Importance of sequence, interval, drug dose, and temperature

“…Clinically, the possibility of combining chemotherapy with local heating therefore looks more attractive. In fact, clinical phase 1-11 studies are already being performed investigating the combined action of local hyperthermia and cisplatin (3, [5][6][7].…”