Phase II trial of oral rubitecan in previously treated pancreatic cancer patients
Phase II trial of oral rubitecan in previously treated pancreatic cancer patients
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DOI：
10.1634/theoncologist.10-3-183
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发表时间：
2005-03-01
期刊：
影响因子：
5.8
通讯作者：
Staddon, A
中科院分区：
文献类型：
--
作者：
Burris, HA;Rivkin, S;Staddon, A
背景。局部晚期或转移性胰腺癌需要额外的全身治疗，因为目前的治疗方案只能产生适度的生存益处。Rubitecan (Orathecin， TM)；Supergen Inc., Dublin， CA, http://www.supergen.com)是一种口服活性喜树碱衍生物，在早期临床试验中证明对胰腺癌患者有疗效。该II期开放标签试验旨在评估rubitecan对传统化疗难治的局部晚期或转移性胰腺癌患者的安全性和有效性。58例在接受至少一种化疗方案后失败或复发的晚期胰腺癌患者入组，接受连续8周的鲁比特康治疗，剂量为1.5 mg/m(2)，口服，每周连续5天，随后休息2天，重复。主要终点为有效率。进展时间、总生存期、CA19-9水平的变化和临床获益反应的综合测量作为次要终点进行评估。在43例可测量疾病的患者中，7%（3/43）达到部分缓解，16%（7/43）达到疾病稳定，总体缓解和疾病稳定率为23%。所有反应均经独立放射学检查证实。应答患者的中位生存期比整个研究队列的中位生存期更长（10个月对3个月）。胃肠道和血液学毒性是最常见的不良反应。口服rubitecan对重度预处理的难治性胰腺癌患者产生反应，耐受性良好。口服rubitecan的总体风险-收益概况似乎很有希望，支持在难治性和化疗初治胰腺癌患者的III期试验中进一步评估。
Background. Additional systemic treatments for locally advanced or metastatic pancreatic cancer are needed, as current treatment options produce only modest survival benefits. Rubitecan (Orathecin (TM); Supergen Inc., Dublin, CA, http://www.supergen.com) is an orally active camptothecin derivative with demonstrated responses in patients with pancreatic cancer in early clinical trials. This phase II, open-label trial was developed to assess the safety and efficacy of rubitecan in patients with locally advanced or metastatic pancreatic cancer refractory to conventional chemotherapy.Methods. Fifty-eight patients with failed or relapsed advanced pancreatic cancer after receiving at least one prior chemotherapy regimen were enrolled to receive eight consecutive weeks of treatment with rubitecan at a dose of 1.5 mg/m(2) orally on five consecutive days per week, followed by 2 days off therapy, repeatedly. The primary end point was response rate. Time to progression, overall survival, changes in CA19-9 levels, and the composite measure of clinical benefit response were evaluated as secondary end points.Results. Among 43 patients with measurable disease, 7% (3/43) achieved partial responses and 16% (7/43) had disease stabilization for an overall response and disease stabilization rate of 23%. All responses were confirmed by independent radiology review. Median survival was longer in responding patients than in the overall study cohort (10 months versus 3 months). Gastrointestinal and hematologic toxicities were the most commonly reported adverse events.Conclusion. Oral rubitecan produced responses and was well tolerated by heavily pretreated patients with refractory pancreatic cancer. The overall risk-benefit profile of oral rubitecan appears promising, supporting further evaluation in phase III trials in patients with refractory and chemotherapy-naive pancreatic cancer.