A Phase I Multicenter Study of Continuous Oral Administration of Lonafarnib (SCH 66336) and Intravenous Gemcitabine in Patients With Advanced Cancer

Abstract

We conducted a phase I study to assess safety, pharmacokinetics, pharmacodynamics, and activity of lonafarnib plus gemcitabine. Subjects received oral lonafarnib twice daily and gemcitabine on days 1, 8, and 15 every 28 days; multiple dose levels were explored. Lonafarnib had no apparent effect on gemcitabine PK. Mean lonafarnib half-life ranged from 4 to 7 hr; median T_max values ranged from 4 to 8 hr. Two patients had partial response; seven patients had stable disease at least 6 months. Oral lonafarnib at 150 mg a.m./100 mg p.m. plus gemcitabine at 1,000 mg/m² is the maximum tolerated dose with acceptable safety and tolerability.

Keywords: :

• Lonafarnib
• Gemcitabine
• Phase I
• Advanced cancer

ACKNOWLEDGMENTS

This work was supported by Merck & Company, formerly known as Schering-Plough Research Institute. We gratefully acknowledge the invaluable contributions of the patients who participated in this study and their families. We also gratefully acknowledge the research clinical teams and health care providers at Duke, UCLA, and Mayo clinic who participated in this clinical study.