Cancer Chemother Pharmacol (1994) 33:355 - 357 ancer hemotherapy and harmacology 9 Springer-Verlag 1994 Short communication High-dose VP16 cisplatinum in soft tissue sarcoma of children M. Grabois, D. Frappaz, E. Bouffet, C. Carrie, D. Bouhour, T. Philip, M. Brunat-Mentigny Pediatric Department of Centre Leon Berard 28, Rue Laennec, F-69373 Lyon, France Received 6 May 1993/Accepted 15 September 1993 Abstract. Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with initial metastatic disease, (one patient, partial response, one patient), refractory pri- mary, (two patients, relapse, five patients) were treated with a combination of high-dose VP16 (100 mg/m 2 daily for 5 days) and cisplatin (40 mg/m 2 daily for 5 days). The response rate was five out of nine or 55% (__ 32%) (two complete and three partial, responses). Three of the five responders had rhabdomyosarcomas. The duration of response was 4-58 months (median 11 months). The toxicity was mainly hematological. Thus, the high-dose VP16-cisplatin association warrants further evaluation in soft tissue sarcoma in children. Introduction The treatment of soft tissue sarcoma (STS) in childhood is specific for several reasons. Such tumors are usually highly chemosensitive. Moreover, local treatments (surgery and/or radiotherapy) induce major late sequelae that are now re- cognized as unacceptable for the 50% long-term survivors [4, 5, 7, 15]. Major improvement has been achieved with the use of neoadjuvant chemotherapy using vincristine, dactinomycin, doxorubicin, cyclophosphamide (VAC-VAd, VACA) and, more recently, ifosfamide (IVA-IVAd) [10]. With such associations, more than 50% of children with localized STS become long-term survivors without the need for additional aggressive local treatment. For those patients with a poor prognosis (locaiized parameningeal, or initially metastatic disease or relapse after conventional treatments) alternative treatments are required. They may include a multidisciplinary approach associating chemo- radiotherapy and surgery, with or without high-dose che- motherapy followed by autologous bone marrow rescue for Correspondence to: D. Frappaz responders. Several second line therapies have been de- scribed, including VINCAEPI and daily oral low dose VP16 [13, 19]. The goal of this report is to describe an alternative second-line chemotherapy that could be used in STS of childhood. Material and Methods Between April 1987 and February 1992 nine children under 16 years of age with metastatic, recurrent or unresponsive histologically proven STS were treated with etoposide (VP16) and high-dose cisplatin at the Centre Ldon B&ard, Lyon, France. Eligibility requirements for this study included: presence of measurable disease, normal renal function assessed by serum creatinine level, a 3-week interval since any prior chemotherapy, and a life expectancy of at least 6 weeks. Pretreatment investigations included: complete physical examination, measurement of lesions by Ultrasonography or CT scan, chest X-ray, complete blood count, renal and hepatic function tests. Patients. Patients' characteristics are summarized in Table 1. Briefly, there were seven boys and two girls aged 23-186 months at diagnosis (median = 75 months) and 31-235 months at the start of the trial (median = 79 months). Five patients had a rhabdomyosarcoma, two a synovial cell sarcoma, one, hemangiopericytoma and one desmoplastic small round cell tumor. Initial stages were as follows: stage I, one patient: stage II, four patients; stage III, two patients; stage IV, two patients. The status at the start of the trial was as follows: one patient with metastatic disease received the VP 16/CDDP combination as first- line therapy. One patient was in the first PR, two had primarily re- fractory disease, and five patients had relapsed (two untreated, one sensitive, two resistant). Prior therapy included IVA (ifosfamide, vin- cristine, dactinomycin, 2-6 courses) in all eight pretreated patients. Three patients had received 1-2 courses of a carboplatinum-contain- ing regimen (VINCAEPI, vincristine, cal'boplatin, teniposide) and two a doxorubicin-containing regimen. Treatment plan. Patients were hospitalized for treatment. Cisplatin was administered at a dose of 40 mg/m2 daily for 5 days and VP16 at a dose of 100 mg/m2 daily for 5 days, for two cycles, with an interval of 3-4 weeks between each cycle. As previously described [12], cisplatin was infused over a 1-h period in 100-250 ml of 5% dextrose solution with 3% sodium chloride added. Hydration, with normal saline and added potassium chloride (1.5 g/l) was begun 24 h before cisplatin and continued for 7 days (3 l/m2 every 24 h). In addition, 10% calcium chloride 10 mg/m2 per day and 50% magnesium sulfate 5 mg/m2 per