IFOSFAMIDE AND ETOPOSIDE IN CHILDHOOD OSTEOSARCOMA - A PHASE-II STUDYOF THE FRENCH-SOCIETY-OF-PEDIATRIC-ONCOLOGY

The aim of this phase II study was to determine the efficacy of high-d ose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) w ith relapsed or refractory evaluable osteosarcoma were included in a p hase II study of two courses of ifosfamide 3g/m(2)/day and etoposide 7 5 mg/m(2)/day for 4 days. Median age was 14 years (7-19 years). All bu t one had received high-dose methotrexate and doxorubicin as first-lin e treatment. 22 patients had previously received ifosfamide. This regi men was given as first-line in 1 patient, second-line in 23 and third- line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rat e was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the ph ase II regimen as third-line chemotherapy, there was 1 PR. All but 4 p atients had a well tolerated grade 4 neutropenia. Transient mild confu sion or seizures were each observed once. 5 patients are alive 15-31 m onths after the beginning of chemotherapy. This combination of drugs a t this dosage has tolerable toxicity, is efficient and deserves evalua tion in phase III studies. (C) 1997 Elsevier Science Ltd.