Abstract
We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction. Patients and Methods Patients were assigned to one of nine cohorts: cohort 1, bilirubin ≤ upper limit of normal (ULN) and AST ≤ ULN and creatinine clearance (CC) ≥ 60 mL/min; cohort 2, bilirubin more than ULN but ≤ 1.5X ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.5X ULN to ≤ 3X ULN (any AST); cohort 5, CC between 20 and 39 mL/min; cohort 6, bilirubin more than 3X ULN to 10X ULN (any AST); cohort 7, CC less than 20 mL/min; cohort 8, albumin less than 2.5 mg/dL (any bilirubin/AST); and cohort 9, hemodialysis. Sorafenib was administered as a 400-mg dose on day 1 for PK, and continuous daily dosing started on day 8. Results Of 150 registered patients, 138 patients were treated. With the exception of cohorts 6 and 7, at least 12 patients per cohort were assessable, and the dose level with prospectively defined dose-limiting toxicity in less than one third of patients by day 29 was considered tolerable. No significant associations between the sorafenib PK and cohort were found. Conclusion We recommend the following empiric sorafenib starting doses by cohort: cohort 1, 400 mg twice a day; cohort 2, 400 mg twice a day; cohort 3, 400 mg twice a day; cohort 4, 200 mg twice a day; cohort 5, 200 mg twice a day; cohort 6, not even 200 mg every third day tolerable; cohort 7, not defined; cohort 8, 200 mg each day; and cohort 9, 200 mg each day.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1800-1805 |
| Number of pages | 6 |
| Journal | Journal of Clinical Oncology |
| Volume | 27 |
| Issue number | 11 |
| DOIs | |
| State | Published - Apr 10 2009 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Phase i and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction : CALGB 60301. / Miller, Antonius A.; Murry, Daryl J.; Owzar, Kouros; Hollis, Donna R.; Kennedy, Erin B.; Abou-Alfa, Ghassan; Desai, Apurva; Hwang, Jimmy; Villalona-Calero, Miguel A.; Dees, E. Claire; Lewis, Lionel D.; Fakih, Marwan G.; Edelman, Martin J.; Millard, Fred; Frank, Richard C.; Hohl, Raymond J.; Ratain, Mark J.
In: Journal of Clinical Oncology, Vol. 27, No. 11, 10.04.2009, p. 1800-1805.Research output: Contribution to journal › Article
TY - JOUR
T1 - Phase i and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction
T2 - CALGB 60301
AU - Miller, Antonius A.
AU - Murry, Daryl J.
AU - Owzar, Kouros
AU - Hollis, Donna R.
AU - Kennedy, Erin B.
AU - Abou-Alfa, Ghassan
AU - Desai, Apurva
AU - Hwang, Jimmy
AU - Villalona-Calero, Miguel A.
AU - Dees, E. Claire
AU - Lewis, Lionel D.
AU - Fakih, Marwan G.
AU - Edelman, Martin J.
AU - Millard, Fred
AU - Frank, Richard C.
AU - Hohl, Raymond J.
AU - Ratain, Mark J.
PY - 2009/4/10
Y1 - 2009/4/10
N2 - We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction. Patients and Methods Patients were assigned to one of nine cohorts: cohort 1, bilirubin ≤ upper limit of normal (ULN) and AST ≤ ULN and creatinine clearance (CC) ≥ 60 mL/min; cohort 2, bilirubin more than ULN but ≤ 1.5X ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.5X ULN to ≤ 3X ULN (any AST); cohort 5, CC between 20 and 39 mL/min; cohort 6, bilirubin more than 3X ULN to 10X ULN (any AST); cohort 7, CC less than 20 mL/min; cohort 8, albumin less than 2.5 mg/dL (any bilirubin/AST); and cohort 9, hemodialysis. Sorafenib was administered as a 400-mg dose on day 1 for PK, and continuous daily dosing started on day 8. Results Of 150 registered patients, 138 patients were treated. With the exception of cohorts 6 and 7, at least 12 patients per cohort were assessable, and the dose level with prospectively defined dose-limiting toxicity in less than one third of patients by day 29 was considered tolerable. No significant associations between the sorafenib PK and cohort were found. Conclusion We recommend the following empiric sorafenib starting doses by cohort: cohort 1, 400 mg twice a day; cohort 2, 400 mg twice a day; cohort 3, 400 mg twice a day; cohort 4, 200 mg twice a day; cohort 5, 200 mg twice a day; cohort 6, not even 200 mg every third day tolerable; cohort 7, not defined; cohort 8, 200 mg each day; and cohort 9, 200 mg each day.
AB - We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction. Patients and Methods Patients were assigned to one of nine cohorts: cohort 1, bilirubin ≤ upper limit of normal (ULN) and AST ≤ ULN and creatinine clearance (CC) ≥ 60 mL/min; cohort 2, bilirubin more than ULN but ≤ 1.5X ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.5X ULN to ≤ 3X ULN (any AST); cohort 5, CC between 20 and 39 mL/min; cohort 6, bilirubin more than 3X ULN to 10X ULN (any AST); cohort 7, CC less than 20 mL/min; cohort 8, albumin less than 2.5 mg/dL (any bilirubin/AST); and cohort 9, hemodialysis. Sorafenib was administered as a 400-mg dose on day 1 for PK, and continuous daily dosing started on day 8. Results Of 150 registered patients, 138 patients were treated. With the exception of cohorts 6 and 7, at least 12 patients per cohort were assessable, and the dose level with prospectively defined dose-limiting toxicity in less than one third of patients by day 29 was considered tolerable. No significant associations between the sorafenib PK and cohort were found. Conclusion We recommend the following empiric sorafenib starting doses by cohort: cohort 1, 400 mg twice a day; cohort 2, 400 mg twice a day; cohort 3, 400 mg twice a day; cohort 4, 200 mg twice a day; cohort 5, 200 mg twice a day; cohort 6, not even 200 mg every third day tolerable; cohort 7, not defined; cohort 8, 200 mg each day; and cohort 9, 200 mg each day.
UR - http://www.scopus.com/inward/record.url?scp=64649083367&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64649083367&partnerID=8YFLogxK
U2 - 10.1200/JCO.2008.20.0931
DO - 10.1200/JCO.2008.20.0931
M3 - Article
C2 - 19255312
AN - SCOPUS:64649083367
VL - 27
SP - 1800
EP - 1805
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 11
ER -