To compare two consecutive treatment programs in metastatic osteosarcoma at presentation. Between 1987 and 1999 treatment of stage IIIB osteosarcoma included induction chemotherapy (CHT) which consisted in 3-5 cycles of intra-arterial doxorubicin (DOX) 75 mg/m2 or cis-platin (CDDP) 120 mg/m2, surgery or definitive local radiation therapy (RT) for primary and adjuvant CHT with DOX, CDDP or HDMTX. Thirty nine patients were included in this protocol. Since 2000 a more intensive induction CHT protocol was adopted. It consisted in 4 cycles of DOX 90 mg/m2 +CDDP 120 mg/m2 (24 patients) or DOX 60 mg/m2 +CDDP 120 mg/m2+Ifosfamide (IFO) 6 g/m2 (7 patients). Adjuvant chemotherapy included DOX, CDDP, IFO or VP-16. Residual lung deposits were removed at the end of adjuvant treatment.Aim
Methods
The purpose of study was to evaluate retrospectively the efficacy of Ifosfamide-Carboplatin containing chemotherapy in recurrent/refractory osteosarcoma and MFH of the extremities. Twenty seven osteosarcoma and 2 MFH pts who had achieved complete surgical remission after multimodal treatment and then progressed soon after en-bloc bone resection or developed recurrent disease were included in two chemotherapy protocols. There were 20M/9F with ages ranging from 15 to 36 yrs (mean 20). Chemotherapy consisted of ifosfamide (median dose per cycle 7.5 g/m2) + carboplatin (median dose 350 mg/m2) + etoposide (median dose 450 mg/m2) – (regimen ICE) or doxorubicin 60 mg/m2 (regimen ICA). Response was evaluated according to RECIST. Survival was calculated from the time of R1 to death and analyzed as February 11, 2009. In total 93 (from 1 to 5. mean 3) cycles were administrated between October 2003 and December 2008. Of 17 ICE pts 3 had PR (17.6%), 10 had SD (58.8%) and 4 (23.5%) – PD. Among 12 ICA pts 3 (25%) had PR, 6 (50%) had SD and 3 (25%) had PD. Sixteen pts (55%) without progression during chemotherapy achieved second surgical remission. At last follow-up 12 pts died of disease, 8 are AWD and 9 are NED. Actuarial 5-year survival was 35±16%, median 38 mos. Outcome was related to relapse-free interval. Five-year survival was 23±18% among patients who relapsed <
12 mos after CR1 and 64±18% among pts who relapsed later, p=0.3. 5-year survival was significantly better in pts in whom chemotherapy was followed by surgery for distant metastases − 37.8±27% (median 38 mos), versus 23.3±19% (median 11 mos.) in patients treated without surgery, p<
0.05. We conclude that retrieval chemotherapy stopped disease progression in the majority of cases. Followed by surgery it was associated with better survival. These regimens and treatment strategy need further investigation in prospective trials.
