Luo Zhiguo, Zhang Xiaowei, Peng Wei, Wu Xianghua, Wang Huijie, Yu Hui, Wang Jialei, Chang Jianhua, Hong Xiaonan
From the Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, shanghai 200032, China.
Medicine (Baltimore). 2015 Oct;94(43):e1777. doi: 10.1097/MD.0000000000001777.
Patients with advanced soft tissue sarcoma (aSTS) typically have a poor prognosis. Patients progressing to doxorubicin-based regimen have limited therapeutic options. Monotherapy with cytotoxic drugs appears to have only modest activity in the second-line setting. The purpose of this phase II study was to prospectively evaluate the safety and efficacy of combination regimen with gemcitabine, vincristine, and cisplatin (GVP) as a salvage treatment for patients with aSTS.Eligible patients were female with 18∼75 years old, and had aSTS that had progressed after 1 prior anthracyclines-based chemotherapy regimen. Patients were treated with 1,000 mg/m gemcitabine intravenously (IV) on days 1 and 8, 1.4 mg/m (max 2 mg) vincristine IV on day 1 and 25 mg/m cisplatin IV on days 1 through 3 every 21 days until disease progression, unacceptable toxicity or up to 6 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), over response rate (ORR) and safety. This trial was registered with http://www.clinicaltrials.gov (no. NCT01192633).A total of 26 patients with a median age 47 years (21-72) were recruited. ORR was 23.1% [1 complete response and 5 partial responses]. The median PFS and OS were 4.8 (95% CI, 0.1-9.5) months and 15.0 (95% CI, 6.1-23.9) months, respectively. Grade 3/4 hematologic toxicities included neutropenia (34.6%), leukopenia (23.1%), thrombocytopenia (11.5%) and anemia (3.8%). No febrile neutropenia and grade 3/4 non-hematologic toxicities occurred. The most frequent non-hematologic toxicities were nausea/vomiting (50.0%), fatigue (30.8%), and fever (11.5%).We conclude that GVP regimen is effective with a favorable safety profile as the second-line chemotherapy in aSTS patients, which warrants further investigation in a phase III study.
晚期软组织肉瘤(aSTS)患者的预后通常较差。进展到基于阿霉素方案的患者治疗选择有限。细胞毒性药物单药治疗在二线治疗中似乎仅有适度活性。这项II期研究的目的是前瞻性评估吉西他滨、长春新碱和顺铂联合方案(GVP)作为aSTS患者挽救治疗的安全性和疗效。符合条件的患者为18至75岁的女性,患有aSTS且在1个先前基于蒽环类药物的化疗方案后病情进展。患者在第1天和第8天接受1000mg/m²吉西他滨静脉注射(IV),第1天接受1.4mg/m²(最大2mg)长春新碱IV,第1天至第3天接受25mg/m²顺铂IV,每21天一次,直至疾病进展、出现不可接受的毒性或最多6个周期。主要终点是无进展生存期(PFS)。次要终点包括总生存期(OS)、总缓解率(ORR)和安全性。该试验已在http://www.clinicaltrials.gov注册(编号NCT01192633)。共招募了26例中位年龄47岁(21 - 72岁)的患者。ORR为23.1%[1例完全缓解和5例部分缓解]。中位PFS和OS分别为4.8(95%CI,0.1 - 9.5)个月和15.0(95%CI,6.1 - 23.9)个月。3/4级血液学毒性包括中性粒细胞减少(34.6%)、白细胞减少(23.1%)、血小板减少(11.5%)和贫血(3.8%)。未发生发热性中性粒细胞减少和3/4级非血液学毒性。最常见的非血液学毒性是恶心/呕吐(50.0%)、疲劳(30.8%)和发热(11.5%)。我们得出结论,GVP方案作为aSTS患者的二线化疗有效且安全性良好,值得在III期研究中进一步研究。