Phase II Trial of Oral Rubitecan in Previously Treated Pancreatic Cancer Patients

Learning Objectives After completing this course, the reader will be able to: Describe the current standard of care for the treatment of advanced pancreatic cancer. State the rationale for treating refractory, advanced pancreatic cancer with the novel oral topoisomerase‐I inhibitor rubitecan. Describe how the phase II trial results of oral rubitecan in pretreated, advanced pancreatic cancer compare with those from prior trials of rubitecan and gemcitabine in advanced pancreatic cancer. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Background. Additional systemic treatments for locally advanced or metastatic pancreatic cancer are needed, as current treatment options produce only modest survival benefits. Rubitecan (Orathecin™; 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/m2 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‐naïve pancreatic cancer.