A phase I II study of combined weekly systemic cisplatin and locoregional hyperthermia in patients with previously irradiated recurrent carcinoma of the uterine cervix

We investigated the feasibility and the anti-tumour activity of weekly cisplatin and the simultaneous application of local hyperthermia in patients with a pelvic recurrence of cervical cancer in previously irradiated area. Dose levels of cisplatin 60 mg m(-2), 70 mg m(-2) and 80 mg m(-2) were studied. Treatment objective of hyperthermia was the achievement of a tumour temperature of greater than or equal to 42 degrees for 60 min, during cisplatin administration. The protocol advised six weekly cycles of combined treatment. Nineteen patients, median age 47 years (range 26-71), were treated. A total of 89 cycles of combined treatment were administered. Even at the highest dose level of cisplatin, 80 mg m(-2) weekly, no dose-limiting toxicity was observed. Leucocytopenia at scheduled retreatment resulted in 1 or 2 weeks postponement in five cases. Neurotoxicity and renal toxicity were mild or absent. Maximum tumour temperatures achieved ranged 39.7-43.6 degrees C, mean 41.6 +/- 0.7 degrees C. All 19 patients were evaluable for response. One patient achieved a complete response that lasted 20 months, and nine patients achieved a partial response for a median duration of 6 months (range 4-50+ months), for an overall response rate of 53%. One patient subsequently underwent salvage surgery and currently remains free of disease at 4 years. We found that this combined hyperthermia-dose-intensive cisplatin regimen was well-tolerated. The true impact of the combination of cisplatin and locoregional hyperthermia can only be answered in a randomized study. Nonetheless, based on existing data on the poor efficacy of cisplatin in pelvic recurrent cervical cancer, we believe that the combined modality approach of weekly hyperthermia plus dose-intensive cisplatin is an attractive regimen, particularly if subsequent salvage surgery is available.