Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial

Purpose: To determine the activity of carboplatin/ifosfamide in patients wi th previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. Patients and Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response war evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, hist ologic response was assessed. Adjuvant therapy comprised two additional car boplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patien ts were stratified at enrollment: stratum A, resectable primary tumor witho ut metastases; stratum B, unresectable primary tumor; and stratum C, metast atic disease at diagnosis. Week 6 response was compared with that of a hist oric group that received only ifosfamide during the initial window evaluati on. Results: The clinical and radiographic response rate to three cycles of car boplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Co mpared with the historic population who received only ifosfamide, the combi nation of carboplatin and ifosfamide reduced the progressive disease rate a t week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year even t-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respec tively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. Conclusion: This pilot trial suggests that carboplatin/ifosfamide combinati on chemotherapy has substantial antitumor activity. In the context of a mul tiagent chemotherapy protocol comprising high-dose methotrexate and doxorub icin, we found that the addition of carboplatin/ifosfamide resulted in pati ent outcomes comparable to trials using cisplatin-based therapy with less l ong-term toxicity. J Clin Oncol 19:171-182. (C) 2001 by American Society of Clinical Oncology.