Osteogenic sarcoma studies by the cancer and leukemia group B

Our group first reported adriamycin (ADR) to be effective in 40% of the patients with pulmonary metastases from osteosarcoma. To determine the efficacy of adjuvant therapy in osteosarcoma without detectable overt metastases, the Cancer and Leukemia Group B (CALGB) initiated a study in 1971 wherein 88 patients were given ADR 2 weeks (median) after surgical excision of the primary lesion. Six courses of ADR (30 mg/m²/day for 3 days) were administered every 4 weeks. Forty six (52.2%) of 88 patients treated had relapsed after a maximum follow-up of more than 72 months. Protocol deviations such as reduction of the ADR dose for leukopenia nadir of more than 1,000/mm³ in 17, transmedullary amputation of involved bone in 17, and inappropriate ADR dose reduction and surgery deviation in 8 resulted in a relapse in 11 (64.7%), 11 (64.7%), and 6 (75%), respectively. In contrast, only 18 (39%) of 46 patients who adhered to ADR dose and radical surgery relapsed. In 1975, CALGB initiated a study to determine whether the disease-free interval and survival of patients with primary osteosarcoma vary depending on whether patients are administered ADR alone or alternating ADR and high-dose methotrexate followed by citrovorum factor rescue (HDMTX-CFR). Within a month after surgery, 62 patients with operable primary osteosarcoma were randomized to receive either 1) 30 mg ADR/m²/day for 3 successive days every 4 weeks for 6 courses, or 2) 30 mg ADR/m²/day for 3 successive days twice, 4 weeks apart, followed by a 200-mg HDMTX/kg iv infusion for 6 hours succeeded by 12 mg CF im every 6 hours for 12 doses oruntil the plasma MTX level reached 10^-7 M or until at 3-week intervals. Thereafter, 2 courses each of ADR and the HDMTX-CF cycle were alternately repeated for a total of 6 courses for each agent. After a follow-up period that ranged from 1 to 36 months (mean, 12 mo), interim life-table estimates showed 50% of all patients were free of disease at 2 years. Cases continue to accrue, and the treatment arms remain blinded. These preliminary results indicated that ADR given alone was as effective as alternating courses of ADR and HDMTX-CF in preventing early disease recurrence in patients with operable primary osteosarcoma.