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

Abstract

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.

Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

“…[24][25][26][27] The doxorubicin/cisplatin/HD-MTX (MAP) regimen is most frequently used as front-line ChT in children and young adult patients; [24][25][26] however, HD-MTX can be challenging to administer in adults. 27,28 In patients aged over 40 years, the use of MTX (8 g/m 2 ) after a poor response to non-MTX induction ChT was proved to be feasible, and regimens combining doxorubicin, cisplatin and potentially ifosfamide are an alternative. [24][25][26]29 Most current protocols for localised disease include a period of preoperative ChT, to facilitate local surgical treatment and to allow the assessment of histological response, although there is no evidence to support a change in ChT based on this alone .…”

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies

“…The M-EI protocol is based on the randomized OS94 paediatric trial, which demonstrated that children and adolescent osteosarcoma patients receiving M-EI had a similar outcome as those receiving methotrexate combined with doxorubicin [128]. The adult API-AI protocol is based on a phase II trial showing that the API-AI group had similar response rates as a group receiving API-AI plus HDMTX [133], with similar findings reported in a phase III trial [134]. A recent French study reported that the M-EI and API-AI protocols yielded similar survival outcomes in 18-to 25-year-old patients, though histological response was better in the M-EI group (60%) than the API-AI group (41%) [132].…”

Resource‐appropriate selection of osteosarcoma treatment protocols in low‐ and middle‐income countries

“…Centers reported 5‐year relapse/progression‐free (PFS) survival rates in patients with osteosarcoma ranging from 40% to 68% with various combinations of the other active drugs (Figure 3A,B; Table 3). 7,8,42–61 The initial proof of non‐HDMTX protocols came from the European Osteosarcoma Intergroup (EOI) trials. While the first EOI trial compared two‐drug protocol Adriamycin‐ cisplatin (AP) to AP with HDMTX, the second trial compared AP to a T10‐like multidrug protocol 48,62 .…”

“…The other non‐HDMTX protocols (Table 3) are the French AP–ifosfamide (API)‐Adriamycin ifosfamide (AI) 56,57 ; German AP–vincristine (V)‐cyclophosphamide (CTX) 55 ; the MD Anderson AP–AI (good responders) with additional HDMTX (poor responders) 64 ; the St. Judes OS99 and OS91 with ifosfamide Adriamycin (IA)–carboplatin (C) and IA–C with HDMTX 53,65 ; and Brazilian IC–epirubicin(Epi)) with HDMTX for poor responders and AP alternating with high‐dose ifosfamide 59, 66 and other Epi‐based protocols 67 …”