Bupathi Manojkumar, Hays John L, Chen James L
Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, Ohio, United States of America.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2017 Nov 15;12(11):e0188116. doi: 10.1371/journal.pone.0188116. eCollection 2017.
Sarcomas are rare, heterogeneous tumors for which prognosis remains dismal in patients with advanced disease. Pazopanib, a vascular endothelial growth factor receptor inhibitor, has shown modest efficacy in patients with soft tissue sarcoma who fail cytotoxic chemotherapy. The cytotoxic agent temozolomide has also demonstrated activity in patients with advanced sarcoma.
We performed a retrospective case series to evaluate the feasibility of adding temozolomide to pazopanib in advanced sarcoma patients following single-agent pazopanib failure.
Patients with recurrent, metastatic sarcomas who had progressed on single-agent pazopanib and continued on pazopanib with the addition of temozolomide were included in this retrospective analysis to examine the tolerability and responses associated with the treatment combination.
Nine patients with a range of sarcoma subtypes were identified (55% female; median age, 48 years; median number of therapies prior to pazopanib, 3). All patients received combination therapy. One patient was recently started on therapy and was excluded from the analysis (n = 8 evaluable patients). Median PFS for single-agent pazopanib was 7.5 months (range 2-19). For the eight evaluable patients (63% female), best response at 4 months with pazopanib plus temozolomide was partial response (n = 1), stable disease (n = 3) and progressive disease (n = 4), with a median PFS of 3.5 months (range 0-15). Median PFS with combination treatment in patients with stable disease or response was 8 months (range 5-15). All four patients who achieved clinical benefit remain on therapy and are tolerating the combination therapy with expected but manageable side effects.
In heavily pretreated patients with advanced sarcoma, the addition of temozolomide to pazopanib was found to be tolerable. Future prospective trials are required to deduce whether temozolomide extends the clinical benefit of pazopanib.
肉瘤是一种罕见的异质性肿瘤，晚期患者的预后仍然很差。帕唑帕尼是一种血管内皮生长因子受体抑制剂，对接受细胞毒性化疗失败的软组织肉瘤患者显示出一定疗效。细胞毒性药物替莫唑胺在晚期肉瘤患者中也表现出活性。
我们进行了一项回顾性病例系列研究，以评估在晚期肉瘤患者单药帕唑帕尼治疗失败后加用替莫唑胺的可行性。
本回顾性分析纳入了复发性、转移性肉瘤患者，这些患者在单药帕唑帕尼治疗期间病情进展，之后继续使用帕唑帕尼并加用替莫唑胺，以检查该联合治疗的耐受性和反应。
确定了9例肉瘤亚型各异的患者（55%为女性；中位年龄48岁；帕唑帕尼治疗前的中位治疗次数为3次）。所有患者均接受了联合治疗。1例患者最近开始治疗，被排除在分析之外（n = 8例可评估患者）。单药帕唑帕尼的中位无进展生存期为7.5个月（范围2 - 19个月）。对于8例可评估患者（63%为女性），帕唑帕尼加替莫唑胺治疗4个月时的最佳反应为部分缓解（n = 1）、疾病稳定（n = 3）和疾病进展（n = 4），中位无进展生存期为3.5个月（范围0 - 15个月）。病情稳定或有反应的患者联合治疗的中位无进展生存期为8个月（范围5 - 15个月）。所有4例获得临床益处的患者仍在接受治疗，并且能够耐受联合治疗，副作用预期但可控。
在接受过大量治疗的晚期肉瘤患者中，发现帕唑帕尼加用替莫唑胺是可耐受的。需要未来的前瞻性试验来推断替莫唑胺是否能延长帕唑帕尼的临床益处。
