Results of API–AI based regimen in osteosarcoma adult patients included in the French OS2006/Sarcome-09 study

In the OS2006 study, patients younger than 18 years were treated with a methotrexate-based regimen (MTX), patients older than 25 years with a doxorubicin–cisplatin–ifosfamide-based regimen (API–AI), whereas patients aged 18–25 years received either API–AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API–AI. Preoperative chemotherapy combined three doxorubicin–ifosfamide–cisplatin (API) and two doxorubicin–ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin–ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide–ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18–67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety-six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28–48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow-up of 4.8 years, the 5-year event-free survival and overall survival rates were 46% (95% CI 36–56) and 57% (95% CI 47–67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API–AI proved feasible with no excess of toxicity, and favourable activity despite poor-prognosis factors.