Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma

Osteosarcoma is one of the most common juvenile malignant turners in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage sur gery + adjuvant therapy) improved the patients' overall survival and qualit y of life. We evaluated the efficacy and feasibility of pre-operative chemo therapy with intra-arterial (IA) cisplatin plus continuous intravenous infu sion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence p attern and the survival impact based on the histologic response of pre-oper ative chemotherapy. Fourty-one patients with histologically-proven high gra de osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m(2) IA and adriamycin 7 5 mg/ m(2)/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histol ogic tumor response, if the tumor necrosis was >90%, the same regimen was a dministered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfam ide 7.5 gm/m(2)/5 d IV + high dose MTX 10 gm/m(2) IV+VP-16 360 mg/m(2)/3 d IV) was administered every 3-weeks for 6 cycles if the tumor necrosis was < 90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities , because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty one p atients were male and 16 were female with median age of 16 years (range 8-4 1). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of n eutropenic sepsis, completed the planned pre-operative therapy. Of the 36 p atients who received surgery, limb salvage surgery was possible in 30 patie nts (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27. 8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disea se-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No opera tion-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with su pportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by s urgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To im prove the survival rate, the possible role of good salvage chemotherapy wit h a non-cross resistance regimen in poor responders should be evaluated.