A phase I multicenter study of continuous oral administration of lonafarnib (SCH 66336) and intravenous gemcitabine in patients with advanced cancer.
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/m(2) is the maximum tolerated dose with acceptable safety and tolerability.
Duke University Medical Center, Durham, North Carolina, USA.
Nan Soon
NS
Wong
Kellen L
KL
Meadows
Lee S
LS
Rosen
Alex A
AA
Adjei
Scott H
SH
Kaufmann
Michael A
MA
Morse
William P
WP
Petros
Yali
Y
Zhu
Paul
P
Statkevich
David L
DL
Cutler
Michael L
ML
Meyers
Herbert I
HI
Hurwitz
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000093542:Gemcitabine; D003986:Dibenzocycloheptenes
D003841:Deoxycytidine; D010880:Piperidines; D011725:Pyridines; D000093542:Gemcitabine; C115354:lonafarnib; D003986:Dibenzocycloheptenes