Journal of Clinical Oncology, Vol 16, 658-663, Copyright © 1998 by American Society of Clinical Oncology
Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin
G Bacci, S Ferrari, N Delepine, F Bertoni, P Picci, M Mercuri, P Bacchini, A Brach del Prever, A Tienghi, A Comandone and M Campanacci
Service de Pediatrie, Medecin Interne Oncologique, Hopital Robert Debre, Paris, France. stafflab@oncolabvrizzoli.tizeta.it
PURPOSE: In osteosarcoma of the extremity, a strong correlation between
chemotherapy-induced necrosis and prognosis has been reported. The aim of
this study was to investigate the possible factors that influence
histologic response to primary chemotherapy. PATIENTS AND METHODS: In 272
patients with high-grade osteosarcoma of the extremity preoperatively
treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and
doxorubicin (ADM), the histologic response to chemotherapy was evaluated
and graded as complete (no viable tumor cells) or incomplete (persistence
of viable tumor cells). Several factors, such as metastatic disease to the
lung at diagnosis, sex, age, site and tumor volume, histologic subtype,
serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate
(MTX) pharmacokinetics were investigated to test their predictive
significance on histologic response. RESULTS: Fifty-one patients with
localized disease (20.6%) and none of the 25 patients with metastatic
disease at presentation had a complete histologic response (P = .006).
After multivariate analysis, performed on patients with localized disease
only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were
proven to be significant predictive factors of histologic response. A
complete response was seen in 28.8% of patients with 700 micromol/L or
greater MTX serum levels and in 9.9% of those patients with lower levels (P
= .001). The chondroblastic subtype was less responsive (6.1% of complete
response), compared with the osteoblastic (16.3%), fibroblastic (33.3%),
and telangiectatic (42.3%). CONCLUSION: Patients with metastatic
osteosarcoma and localized chondroblastic osteosarcoma have a reduced
chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum
peak significantly influences tumor necrosis. A dose adaptation of MTX is
recommended to obtain a serum peak of 700 micromol/L or greater when MTX is
infused in 6 hours.
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