Phase II trial of oral rubitecan in previously treated pancreatic cancer patients.

Abstract

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-naive pancreatic cancer.

• Authors: Howard A Burris 3rd, Saul Rivkin, Robert Reynolds, Jules Harris, Arnold Wax, Hal Gerstein, Karl L Mettinger, Arthur Staddon
• Journal: The oncologist (Oncologist) Vol. 10 Issue 3 Pg. 183-90 (Mar 2005) ISSN: 1083-7159 [Print] England
• PMID: 15793221 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• rubitecan
• Camptothecin

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Disease Progression
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, pathology)
• Survival Analysis