Department of Oncology, Hospital Sant Joan de Déu, Barcelona, Spain.
Pediatr Blood Cancer. 2011 Jul 15;57(1):69-75. doi: 10.1002/pbc.22813. Epub 2011 Mar 7.
Reported overall survival (OS) rates of patients with localized Ewing sarcoma family of tumors (ESFT) are >80% when treated with the MSKCC P6 protocol. However, it has been associated with a 5.8% incidence of secondary leukemias. A modified P6 (mP6) protocol with reduced exposure to chemotherapy is presented.
Thirty-one newly diagnosed ESFT patients were enrolled onto this phase II, single-arm, non-randomized protocol. Courses 1, 2 and 4 consisted of cyclophosphamide 4.2 g/m², doxorubicin 75 mg/m², and vincristine 2 mg/m² (CDV). Cycles 3 and 5 consisted of ifosfamide 9 g/m² and etoposide 500 mg/m² (IE). Course 5 ifosfamide was 14 g/m² if necrosis was <90%.
Twenty-four patients had loco-regional disease and seven had metastases. The 4-year event-free survival (EFS) rate for patients with localized tumors is 83% and overall survival (OS) is 92%. The 3-year EFS rate for patients with distant metastases is 28% and OS rate is 42%. EWS-FLI1 fusion genes were detected in 17 cases (74%) and EWS-ERG in six cases (26%). Type 1 EWS-FLI1 variant was present in 6/7 metastatic patients and 3/16 loco-regional cases (P = 0.001). None of the patients experienced tumor progression before remission. All relapses occurred within 2 years from the end of treatment and local relapses (n = 3) happened in patients who did not receive radiation therapy. No secondary malignancies have been observed, median follow-up of 4.3 years for surviving patients.
In this pilot study, the mP6 protocol produced a complete remission rate of 83% at 4 years in non-metastatic ESFT reducing the risk of secondary malignancies.
采用 MSKCC P6 方案治疗局限性尤文肉瘤家族肿瘤（ESFT）患者的总生存率（OS）超过 80%。然而，该方案与 5.8%的继发性白血病发生率相关。本研究提出了一种改良 P6（mP6）方案，该方案减少了化疗药物的暴露。
31 例新诊断的 ESFT 患者入组本研究，该研究为 II 期、单臂、非随机试验。第 1、2 和 4 个疗程包含环磷酰胺 4.2 g/m²、多柔比星 75 mg/m²和长春新碱 2 mg/m²（CDV）。第 3 和 5 个疗程包含异环磷酰胺 9 g/m²和顺铂 500 mg/m²（IE）。如果坏死<90%，第 5 个疗程的异环磷酰胺剂量为 14 g/m²。
24 例患者有局限性疾病，7 例患者有远处转移。局限性肿瘤患者的 4 年无事件生存率（EFS）为 83%，总生存率（OS）为 92%。远处转移患者的 3 年 EFS 率为 28%，OS 率为 42%。17 例（74%）患者存在 EWS-FLI1 融合基因，6 例（26%）患者存在 EWS-ERG。6/7 例转移性患者和 3/16 例局限性患者存在 EWS-FLI1 类型 1 变体（P = 0.001）。所有患者在缓解前均未出现肿瘤进展。所有复发均发生在治疗结束后 2 年内，且局部复发（n = 3）发生在未接受放疗的患者中。无继发性恶性肿瘤发生，中位随访时间为 4.3 年。
在这项初步研究中，mP6 方案使非转移性 ESFT 患者的完全缓解率在 4 年内达到了 83%，降低了继发性恶性肿瘤的风险。
