Short-Term Efficacy and Safety of Pazopanib Combined with Chemotherapy in Treatment of Advanced Synovial Sarcoma
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摘要:目的
探讨培唑帕尼联合化疗治疗晚期滑膜肉瘤（SS）的近期疗效及安全性。
方法回顾性分析接受培唑帕尼联合不同化疗方案治疗的晚期滑膜肉瘤患者64例，其中，采取一线化疗方案26例、二线化疗方案19例、三线化疗方案19例，对不同方案的治疗效果和安全性进行评价。
结果64例患者中，33例患者部分缓解，12例患者疾病稳定，19例患者疾病进展，其客观缓解率（ORR）和疾病控制率（DCR）分别为51.6%（33/64）和70.3%（45/64），中位PFS为7.55个月（95%CI：6.320~8.780）。采用一线化疗方案的26例患者ORR为65.4%（17/26），DCR为73.1%（19/26），中位PFS为9.167个月（95%CI：6.362~11.971）；采用二线化疗方案的19例患者ORR为47.4%（9/19），DCR为73.7%（14/19），中位PFS为7.55月（95%CI：6.054~9.046）；三线化疗方案的19例患者ORR为36.8%（7/19），DCR为63.2%（12/19），中位PFS为6.09月（95%CI：3.158~9.022）。不良反应以Ⅰ/Ⅱ级为主，Ⅲ/Ⅳ级不良事件很少出现，治疗过程中没有死亡案例。
结论培唑帕尼联合化疗治疗晚期滑膜肉瘤的疗效较好，不良反应可以接受。
Abstract:ObjectiveTo investigate the short-term efficacy and safety of pazopanib combined with chemotherapy in the treatment of advanced synovial sarcoma (SS).
MethodsA total of 64 patients with advanced SS treated with pazopanib combined with different chemotherapy regimens were selected. Among them, 26 patients received first-line chemotherapy regimen, 19 patients received second-line chemotherapy regimen, and 19 patients received third-line chemotherapy regimen. The therapeutic efficacy and safety of different treatment regimens were evaluated.
ResultsOut of the 64 patients, 33 achieved partial response (PR), 12 had stable disease (SD), and 19 experienced progression disease (PD). The objective response rate (ORR) and disease control rate (DCR) were 51.6% (33/64) and 70.3% (45/64), respectively, with a median progression-free survival (PFS) of 7.55 months (95%CI: 6.320–8.780 months). Among the 26 patients treated with the first-line chemotherapy regimen, the ORR was 65.4% (17/26), the DCR was 73.1% (19/26), and the median PFS was 9.167 months (95%CI: 6.362–11.971 months). For the 19 patients receiving second-line chemotherapy regimen, the ORR was 47.4% (9/19), the DCR was 73.7% (14/19), and the median PFS was 7.55 months (95%CI: 6.054–9.046 months). Among the 19 patients treated with the third-line chemotherapy regimen, the ORR was 36.8% (7/19), the DCR was 63.2% (12/19), and the median PFS was 6.09 months (95%CI: 3.158–9.022 months). The majority of adverse events were grade Ⅰ/Ⅱ, whereas grade Ⅲ/Ⅳ adverse events rarely occurred. No deaths occurred during the course of treatment.
ConclusionPazopanib combined with chemotherapy shows good efficacy in the treatment of advanced SS, with acceptable adverse events.
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Key words:
- Synovial sarcoma /
- Pazopanib /
- Molecular targeted therapy /
- Chemotherapy
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Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：王 晶：数据整理，统计分析，文献调研，论文撰写林 峰：研究指导，论文修改
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图 1 滑膜肉瘤患者无疾病进展生存期曲线
Figure 1 Progression-free survival curve of patients with synovial sarcoma
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图 2 滑膜肉瘤患者不同化疗方案的PFS对比曲线
Figure 2 Curves of progression-free survival for patients with synovial sarcoma undergoing different chemotherapy regimens
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图 3 滑膜肉瘤患者不同性别(A)、不同年龄(B)和是否存在肺转移(C)的PFS对比曲线
Figure 3 Curves of progression-free survival for patients with synovial sarcoma stratified by gender (A), age (B) and presence or absence of lung metastasis (C)
表 1 晚期滑膜肉瘤患者的一般特征（N=64）
Table 1 Characteristics of patients with advanced synovial sarcoma (N=64)
Characteristics n (%) Gender Male 40 (62.5) Female 24 (37.5) Age (years) ≥40 27 (42.2) <40 37 (57.8) ECOG 0 42 (65.6) 1 22 (34.4) Primary tumor sites Head-neck 14 (21.9) Limbs 24 (37.5) Trunk 26 (40.6) Metastasis sites Lung 34 (53.1) Lymph node 18 (28.1) Bone 5 (7.8) Adrenal gland 3 (4.7) Spermatic cord 2 (3.1) Intestinal tract 2 (3.1) Chemotherapy regimen First line 26 (40.6) Second line 19 (29.7) Third line 19 (29.7) Treatment Surgery 64 (100.0) Radiotherapy 50 (78.1) Chemotherapy 64 (100.0) 
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表 2 滑膜肉瘤患者生存预后相关因素分析结果
Table 2 Analysis results of prognostic factors related to survival of synovial sarcoma patients
Variable Survival Univariate analysis Multivariate analysis PFS (months) 95%CI χ2 P HR 95%CI P Chemotherapy regimen First line 9.167 6.362–11.971 10.395 0.006 Ref Second line 7.550 6.054–9.046 1.604 0.815–3.160 0.172 Third line 6.090 3.158–9.022 4.020 1.721–9.396 0.001 Gender Female 7.770 6.127–9.413 0.125 0.723 0.836 Ref Male 7.230 5.841–8.619 0.445–1.569 0.576 Age (years) <40 7.430 5.735–9.125 0.039 0.844 0.981 Ref ≥40 7.550 5.627–9.473 0.547–1.761 0.949 Lung metastasis No 9.767 5.616–13.918 1.969 0.161 1.575 Ref Yes 6.660 4.951–8.369 0.868–2.858 0.135
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表 3 所有接受治疗的滑膜肉瘤患者不良反应汇总（n(%)）
Table 3 Summary of adverse events in all treated patients with synovial sarcoma (n(%))
Adverse events Grade Ⅰ/Ⅱ Grade Ⅲ/Ⅳ Total Fatigue 20 (31.25) 2 (3.13) 22 (34.38) Hand-foot syndrome 11 (17.19) 2 (3.13) 13 (20.31) Nausea/vomiting 14 (21.88) 0 (0.00) 14 (21.88) Diarrhea 23 (35.93) 5 (7.81) 28 (43.75) Stomatitis 8 (12.50) 0 (0.00) 8 (12.50) Hypertension 14 (21.88) 0 (0.00) 14 (21.88) Edema 5 (7.81) 0 (0.00) 5 (7.81) Lightening of skin color 8 (12.50) 0 (0.00) 8 (12.50) Change in hair color 34 (53.13) 0 (0.00) 34 (53.13) Leucopenia 23 (35.94) 2 (3.13) 25 (39.06) Thrombocytopenia 26 (40.63) 5 (7.81) 31 (48.44) Anemia 29 (45.31) 0 (0.00) 29 (45.31) Liver function impairment 14 (21.88) 0 (0.00) 14 (21.88) Kidney function impairment 8 (12.50) 0 (0.00) 8 (12.50) Hypothyroidism 11 (17.19) 0 (0.00) 11 (17.19)
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