Rha S Y, Chung H C, Gong S J, Shim K Y, Ahn J B, Yang W I, Shin K H, Yoo N C, Kim J H, Roh J K, Lee C I, Kim B S
Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gyu, Seoul, 120-752, Korea.
Oncol Rep. 1999 May-Jun;6(3):631-7. doi: 10.3892/or.6.3.631.
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 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 patients were male and 16 were female with median age of 16 years (range 8-41). 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 neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (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 disease-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 operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.
骨肉瘤是韩国最常见的青少年恶性肿瘤之一。综合治疗模式（术前化疗+保肢手术+辅助治疗）提高了患者的总生存率和生活质量。我们评估了动脉内（IA）顺铂联合阿霉素持续静脉输注（CI）进行术前化疗的疗效和可行性。我们根据术前化疗的组织学反应评估了保肢率、复发模式和生存影响。1990年1月至1995年6月，纳入了41例经组织学证实为四肢高级别骨肉瘤的患者。术前化疗，每3周给予顺铂120mg/m² IA和阿霉素75mg/m²/72h CI，共3个周期，若可能则行保肢手术，否则行截肢手术。根据组织学肿瘤反应，若肿瘤坏死>90%，则给予相同方案3个周期作为辅助治疗。若肿瘤坏死<90%，则每3周给予挽救方案（异环磷酰胺7.5g/m²/5d静脉滴注+大剂量甲氨蝶呤10g/m²静脉滴注+依托泊苷360mg/m²/3d静脉滴注），共6个周期。41例患者中，37例可评估疗效和毒性，因为4例患者在1或2个周期后拒绝化疗。21例为男性，16例为女性，中位年龄16岁（范围8-41岁）。肿瘤部位为：股骨远端20例，胫骨近端8例，肱骨6例，胫骨远端2例，股骨近端1例。除1例死于中性粒细胞减少性败血症外，所有患者均完成了计划的术前治疗。在接受手术的36例患者中，30例（83.3%）可行保肢手术，27例（75%）显示良好反应（Ⅲ级10例；27.8%，Ⅳ级17例；47.2%）。中位随访23个月，3年无病生存率为54.7%，总生存率为78.3%。在15例复发患者中，主要转移部位是肺。未观察到手术相关死亡。大多数患者经历了Ⅲ-Ⅳ级恶心、呕吐和血液学毒性，经支持治疗后可逆转。IA DDP+CI ADR术前化疗后行手术显示组织学肿瘤反应率为75%，保肢率为83%，3年无病生存率为54.7%，且副作用可耐受。为提高生存率，应评估对反应不佳者采用无交叉耐药方案进行良好挽救化疗的可能作用。
