Phase 2 trial of two courses of cyclophosphamide and etoposide for relapsed high‐risk osteosarcoma patients

BACKGROUND: A phase 2 trial was carried out to assess the antineoplastic activity of 2 courses of cyclophosphamide‐etoposide in relapsed osteosarcoma patients. METHODS: Twenty‐six relapsed osteosarcoma patients with a median age of 18.5 years (8.3‐47.1) were enrolled. Seven patients were in first relapse (27%), 11 in second relapse (42%), 7 in third relapse (27%), and 1 in fourth relapse (4%). Eighteen patients had bone metastasis at study entry (69%). Cyclophosphamide was given at 4 g/m2 on Day 1 followed by etoposide at 200 mg/m2 on Days 2, 3, and 4. Second cyclophosphamide and etoposide was planned at 21 days to 28 days from the previous one. The primary endpoint of the study was the clinical benefit at 4 months measured as progression‐free survival. RESULTS: Progression‐free survival at 4 months was 42%. Five patients achieved responses (19%), 9 patients had stable disease (35%), and 12 had tumor progression (46%). Overall survival (OS) at 1 year was 50%. The only grade 4 extrahematological toxicities were fever (5%), acute bronchospasm (4%) and stomatitis (18%). Six patients (23%) underwent radical surgery after cyclophosphamide and etoposide ×2. CONCLUSIONS: Cyclophosphamide and etoposide ×2 may arrest osteosarcoma progression in a significant number of patients (54%). Osteosarcoma progression arrest after cyclophosphamide and etoposide ×2 translates in a better OS. Cyclophosphamide and etoposide ×2 had good tolerability and the toxicity was time‐limited and resolved in all cases. Cancer 2009. © 2009 American Cancer Society. Twenty‐six relapsed osteosarcoma patients (median age of 18.5 years) were enrolled in a phase 2 trial starting with 2 courses of cyclophosphamide and etoposide (×2). After cyclophosphamide and etoposide ×2, a significant number of patients had osteosarcoma progression arrest (54%). Overall survival at 1 year was 50% (responders 78% vs nonresponders 18%, P .009).