In an attempt to shrink primary osteogenic sarcoma and allow complete surgical removal of the primary tumor, without amputating the involved limb, intensive preoperative chemotherapy with high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (ADR) was initiated in 20 patients with biopsy-proven primary osteogenic sarcoma of the distal femur (15 patients) and proximal tibia (five patients). Following intensive chemotherapy, en bloc resection of the primary tumor with prosthetic replacement of the involved bone was planned. After surgery, adjuvant chemotherapy, consisting of HDMTX with CFR, ADR, and high dose cyclophosphamide was given sequentially for 1 year. Of 20 patients with primary osteogenic sarcoma (two with evidence of pulmonary metastases), 18 had primary tumors that could be clinically measured. Of these 18, 17 demonstrated a decrease in the size of primary tumor prior to surgery, while on chemotherapy. To date, 12 of these patients with osteogenic sarcoma of the distal femur have had total femur and knee joint replacement, and three patients with osteogenic sarcoma of the proximal tibia have had total knee replacement. In all 15 patients, surgical margins were grossly and microscopically free of tumor. There has been no evidence of soft tissue recurrence in any of the 15 patients who have undergone surgery for from 2 to 15 months postoperatively. These preliminary results indicate that with the use of aggressive chemotherapy, it is possible to demonstrate objective tumor regression in primary osteogenic sarcoma, allowing the surgeon to perform en bloc resection of tumor and prosthetic replacement of the involved bone. Although the limb is preserved, it is important to stress that extensive surgery yielding tumor-free margins is performed. The ultimate evaluation of this approach to the treatment of primary osteogenic sarcoma awaits longer observation, to determine limb function and the continued disease-free status, once adjuvant chemotherapy is discontinued.
Thirteen patients with osteogenic sarcoma were treated with multiple drug chemotherapy consisting of bleomycin, cyclophosphamide and dactinomycin. The dosage schedule used was: bleomycin 12 mg/m2/day, cyclophosphamide 600 mg/m2/day, and dactinomycin 450 microgram/m2/day. All drugs were given intravenously for two consecutive days. Treatment was repeated every 2 weeks. Toxicity included severe nausea and vomiting (managed with antiemetics and intravenous hydration) and manifestations of bone marrow depression. Of 13 patients, eight were previously treated with high dose methotrexate with citrovorum factor rescue, cyclophosphamide and Adriamycin. Of these eight, three patients had objective evidence of tumor regression (37.5%). Five of five previously untreated patients had objective evidence of tumor regression. The overall response rate in osteogenic sarcoma patients to BCD was 61.5%. The combination of BCD appears to be more active against osteogenic sarcoma than cyclophosphamide alone or Adriamycin alone. The relative safety with which BCD can be administered makes this combination a valuable adjunct to high dose methotrexate with citrovorum factor rescue and Adriamycin in the treatment of osteogenic sarcoma.
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