The role of ifosfamide in paediatric soft tissue sarcomas

Abstract

Early clinical trials in adults showed favourable results of ifosfamide (IF) in several tumours. In a previous study we used IF and vincristine (VCR) and observed 6 complete responses (CR) among 25 previously heavily treated children. Especially patients with rhabdomyosarcoma (RMS) responded well, with 4 partial responses (PR) and 2 CR among 6 patients. This and the fact that the combination of VCR, actinomycin D (ACD) and cyclophosphamide (CYT) still give good results in RMS patients led us to replace CYT with IF in this combination. This IVA protocol consists of IF 3000 mg/m2 i.v. in 1 h on days 1 and 2, VCR 1.5 mg/m2 by i.v. push on day 1, and ACD 900 micrograms/m2 by i.v. push on days 1 and 2. The course is repeated at 28-day intervals. VCR 1.5 mg/m2 is given on day 14. We used this protocol als induction therapy in 18 newly diagnosed RMS patients. The primary sites were: abdomen (4 patients), bladder and prostate (3), head and neck (9: orbita 5), extremity (1), chest wall (1). At diagnosis, 9 patients had stage I, 4 stage II and 5 stage IV disease. Except for one mixed mesodermal type, all were of the embryonal type. The patients age at diagnosis varied from 2 to 16 years. After three courses, in some patients surgery was performed if radical tumour extirpation seemed possible. The first evaluation took place after three courses. At this point one patient had no response, one had a reduction in tumour mass of less than 50% (partial response PR), 9 patients had greater than 50% tumour-reduction (good partial response [GPR]), and 7 were in complete remission (CR). In 2 of these 7 (CR) no tumour was found on histopathological examination of the specimen. In patients with GPR or CR therapy was continued for 6 months and then stopped. Thirteen patients have been disease-free for 1-20 months from the date of CR. Four patients relapsed 4, 6, 11 and 11 months after CR. There was one therapy-related death. Except for this patient no major toxicity was encountered. These results indicate that by replacing CYT with IF, remission induction can be improved with a major contribution to survival and to enhanced quality of life in these patients.