Abstract：
BACKGROUND: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up.
METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives.
RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months.
CONCLUSIONS: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.
METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives.
RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months.
CONCLUSIONS: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.
摘要：
背景：我们报告了一项使用异环磷酰胺（IFO）测试CDDP的II期试验（OSAD93），在新辅助阶段没有阿霉素，成人骨肉瘤，随访25年。
方法：这是一项关于IFO和CDDP在局部高级别骨肉瘤患者中的新辅助化疗的多中心II期研究。患者在第4天接受了IFO9g/m2和CDDP100mg/m2的4个术前疗程（SHOC方案），其次是当地治疗。在具有>10%残余肿瘤细胞的患者中,术后添加阿霉素(HOCA方案)。良好的组织学反应（GHR），即≤10%的患者中残留肿瘤细胞>30%，是首要目标。无病生存率（DFS），总生存期(OS)和毒性是次要目标.
结果：从1994年1月至1998年6月，纳入60例患者。年龄中位数为27岁（范围：16-63）。原发肿瘤部位为四肢（76%），树干,头部或颈部（24％）。新辅助SHOC后，3-4级和发热性中性粒细胞减少症，血小板减少症,58%的人再次住院，17%,17％和22％的SHOC课程和76％，28%,47%,47%的HOCA课程，分别。16/60（27.5％）患者获得了GHR。中位随访时间为322个月，5年时DFS和OS分别为51.8%和64.4%。十年后，DFS和OS分别为49.9%和64.4%。25岁时,DFS和OS分别为47.8%和55.9%。没有观察到长期的心脏毒性。300个月后，三名患者出现了第二种恶性肿瘤（一例致命）。
结论：虽然未达到OSAD93的主要终点，这种术前不含阿霉素的方案在局部骨肉瘤中具有优异的长期生存率,且毒性有限.
方法：这是一项关于IFO和CDDP在局部高级别骨肉瘤患者中的新辅助化疗的多中心II期研究。患者在第4天接受了IFO9g/m2和CDDP100mg/m2的4个术前疗程（SHOC方案），其次是当地治疗。在具有>10%残余肿瘤细胞的患者中,术后添加阿霉素(HOCA方案)。良好的组织学反应（GHR），即≤10%的患者中残留肿瘤细胞>30%，是首要目标。无病生存率（DFS），总生存期(OS)和毒性是次要目标.
结果：从1994年1月至1998年6月，纳入60例患者。年龄中位数为27岁（范围：16-63）。原发肿瘤部位为四肢（76%），树干,头部或颈部（24％）。新辅助SHOC后，3-4级和发热性中性粒细胞减少症，血小板减少症,58%的人再次住院，17%,17％和22％的SHOC课程和76％，28%,47%,47%的HOCA课程，分别。16/60（27.5％）患者获得了GHR。中位随访时间为322个月，5年时DFS和OS分别为51.8%和64.4%。十年后，DFS和OS分别为49.9%和64.4%。25岁时,DFS和OS分别为47.8%和55.9%。没有观察到长期的心脏毒性。300个月后，三名患者出现了第二种恶性肿瘤（一例致命）。
结论：虽然未达到OSAD93的主要终点，这种术前不含阿霉素的方案在局部骨肉瘤中具有优异的长期生存率,且毒性有限.
