Centre Léon Bérard, CRCL, Unicancer, Lyon Unicancer & UCBL1, Lyon, France.
Centre Oscar Lambret, Lille, France.
Eur J Cancer. 2024 Sep;208:114228. doi: 10.1016/j.ejca.2024.114228. Epub 2024 Jul 15.
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.
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/m and CDDP 100 mg/m 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.
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.
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.
我们报告了一项 II 期临床试验（OSAD93），在新辅助阶段不使用阿霉素，测试顺铂联合异环磷酰胺治疗成骨肉瘤，随访时间为 25 年。
这是一项多中心 II 期研究，在局部高级成骨肉瘤患者中进行新辅助化疗，采用异环磷酰胺和顺铂。患者在第 4 天接受 4 个术前疗程的异环磷酰胺 9 g/m 和顺铂 100 mg/m（SHOC 方案），然后进行局部治疗。对于 >10%肿瘤细胞残留的患者，术后加用阿霉素（HOCA 方案）。主要终点是良好的组织学反应（GHR），即>30%患者中 ≤10%的肿瘤细胞残留。无病生存（DFS）、总生存（OS）和毒性是次要终点。
1994 年 1 月至 1998 年 6 月，共纳入 60 例患者。中位年龄为 27 岁（范围：16-63 岁）。原发肿瘤部位为四肢（76%）、躯干、头部或颈部（24%）。新辅助 SHOC 后，3 级和 4 级及发热性中性粒细胞减少、血小板减少和再住院的发生率分别为 58%、17%、17%和 22%，HOCA 分别为 76%、28%、47%、47%。60 例患者中有 16 例（27.5%）获得 GHR。中位随访 322 个月，5 年时 DFS 和 OS 分别为 51.8%和 64.4%。10 年时，DFS 和 OS 分别为 49.9%和 64.4%。25 年时，DFS 和 OS 分别为 47.8%和 55.9%。未观察到长期心脏毒性。300 个月后，3 例患者发生第 2 种恶性肿瘤（1 例死亡）。
尽管 OSAD93 的主要终点未达到，但这种新辅助阶段不使用阿霉素的方案在局部成骨肉瘤中导致了极好的长期生存，且毒性有限。
