This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burris, H. A. Articles by Staddon, A. Search for Related Content PubMed PubMed Citation Articles by Burris, H. A., III Articles by Staddon, A.

Original Paper Gastrointestinal Cancer

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

^a The Sarah Cannon Cancer Center, Nashville, Tennessee, USA; ^b Swedish Medical Center, Seattle, Washington, USA; ^c Walt Disney Memorial Hospital, Orlando, Florida, USA; ^d Rush Presbyterian St. Luke’s Hospital, Chicago, Illinois, USA; ^e Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, USA; ^f Cancer Institute of Long Island, Great Neck, New York, USA; ^g Supergen, Inc., Dublin, California, USA; ^h Pennsylvania Hospital, Philadelphia, Pennsylvania, USA

Correspondence: Howard A. Burris, III, M.D., The Sarah Cannon Cancer Center, 250 25th Avenue North, Suite 110, Nashville, Tennessee 37203, USA. Telephone: 615-986-4300; Fax: 615-986-0029; e-mail: hburris{at}tnonc.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^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/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.

Key Words. Pancreatic neoplasms • 9-nitrocamptothecin • Antineoplastic agents • Rubitecan

This article has been cited by other articles:

				D. Laheru, E. Lutz, J. Burke, B. Biedrzycki, S. Solt, B. Onners, I. Tartakovsky, J. Nemunaitis, D. Le, E. Sugar, et al. Allogeneic Granulocyte Macrophage Colony-Stimulating Factor-Secreting Tumor Immunotherapy Alone or in Sequence with Cyclophosphamide for Metastatic Pancreatic Cancer: A Pilot Study of Safety, Feasibility, and Immune Activation Clin. Cancer Res., March 1, 2008; 14(5): 1455 - 1463. [Abstract] [Full Text] [PDF]