PRIMARY CHEMOTHERAPY AND DELAYED SURGERY FOR NONMETASTATIC OSTEOSARCOMA OF THE EXTREMITIES - RESULTS IN 164 PATIENTS PREOPERATIVELY TREATEDWITH HIGH-DOSES OF METHOTREXATE FOLLOWED BY CISPLATIN AND DOXORUBICIN

Background. Neoadjuvant chemotherapy is the most accepted treatment fo r localized osteosarcoma. This has led to a great improvement in limb- sparing surgery and in disease-free survival. Patients with a good res ponse to preoperative chemotherapy showed a higher disease-free surviv al rate. Current studies examine the possibility of patients whose lim bs could be rescued with a poor necrosis and a reduction of the side e ffects related to aggressive treatments. Methods. Between September 19 86 and December 1989, 164 patients entered the second neoadjuvant stud y conducted at the Rizzoli Institute, Bologna, Italy, for non-metastat ic osteosarcoma of the extremities. Preoperative chemotherapy consiste d of two cycles of high-dose methotrexate intravenously (IV) followed by cisplatin intraarterially and doxorubicin IV. After surgery, patien ts classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necr osis) had more chemotherapy, which included ifosfamide and etoposide i n addition to the other three drugs. Results. Limb salvage was perform ed in 83% of cases. At an average follow-up of 54 months (36-76),109 p atients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurren ce. In two of these three patients, metastases followed local recurren ce. The 5-year actuarial continuously disease-free survival rate was 6 3%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease-free survival rate was 71%. Conclusions. With an aggressive ne oadjuvant chemotherapy, it is possible to cure more than 60% of nonmet astatic osteosarcoma of the extremities, avoiding amputation in most c ases. Ifosfamide and etoposide seem to be effective in patients who di d not respond to preoperative chemotherapy.