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

W. H. Meyer, C. B. Pratt, C. A. Poquette, B. N. Rao, D. M. Parham, N. M. Marina, A. S. Pappo, H. H. Mahmoud, J. J. Jenkins, J. Harper, M. Neel, B. D. Fletcher

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86 Scopus citations

Abstract

Purpose: To determine the activity of carboplatin/ifosfamide in patients with 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/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. Results: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. Conclusion: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantia] antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalJournal of Clinical Oncology
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Meyer, W. H., Pratt, C. B., Poquette, C. A., Rao, B. N., Parham, D. M., Marina, N. M., Pappo, A. S., Mahmoud, H. H., Jenkins, J. J., Harper, J., Neel, M., & Fletcher, B. D. (2001). Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial. Journal of Clinical Oncology, 19(1), 171-182. https://doi.org/10.1200/JCO.2001.19.1.171