Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin.
BACKGROUND
Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb-sparing surgery and in disease-free survival. Patients with a good response to preoperative chemotherapy showed a higher disease-free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments.


METHODS
Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non-metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate intravenously (i.v.) followed by cisplatin intraarterially and doxorubicin i.v. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs.


RESULTS
Limb salvage was performed in 83% of cases. At an average follow-up of 54 months (36-76), 109 patients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5-year actuarial continuously disease-free survival rate was 63%, 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 neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.
Bacci
G
G
Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy.
Picci
P
P
Ferrari
S
S
Ruggieri
P
P
Casadei
R
R
Tienghi
A
A
Brach del Prever
A
A
Gherlinzoni
F
F
Mercuri
M
M
Monti
C
C
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005121:Extremities / Q000473:pathology / Q000601:surgery; D005260:Female; D005269:Femur / Q000473:pathology / Q000601:surgery; D006801:Humans; D006811:Humerus / Q000473:pathology / Q000601:surgery; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D011183:Postoperative Complications; D011300:Preoperative Care; D012074:Remission Induction; D015996:Survival Rate; D013977:Tibia / Q000473:pathology / Q000601:surgery
D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate