title: A phase I/II study of combined weekly systemic cisplatin and locoregional hyperthermia in patients with previously irradiated recurrent carcinoma of the uterine cervix.
abstract: 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 > or = 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.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute and University Hospital, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: J
authors.initials: J
authors.lastname: van der Zee
authors.forename: M E
authors.initials: ME
authors.lastname: van der Burg
authors.forename: W H
authors.initials: WH
authors.lastname: Kruit
authors.forename: A
authors.initials: A
authors.lastname: Logmans
authors.forename: G C
authors.initials: GC
authors.lastname: van Rhoon
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D002945:Cisplatin