Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101

Antonius A. Miller, Daryl J. Murry, Kouros Owzar, Donna R. Hollis, Lionel D. Lewis, Hedy L. Kindler, John L. Marshall, Miguel A. Villalona-Calero, Martin J. Edelman, Raymond J. Hohl, Stuart M. Lichtman, Mark J. Ratain

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Purpose: We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction. Patients and Methods: Patients were assigned to one of three cohorts: cohort 1, AST ≥ 3x upper limit of normal; cohort 2, direct bilirubin of 1 to 7 mg/dL; and cohort 3, creatinine of 1.6 to 5.0 mg/dL. Cohort 1a was amended for albumin less than 2.5 g/dL. Erlotinib was administered orally daily to groups of at least three assessable patients in escalating doses of 50, 75, 100, and 150 mg, starting with 50 mg in hepatic dysfunction patients and 75 mg in renal dysfunction patients. Results: Between December 2001 and May 2005, 55 patients were accrued. The distribution of assessable patients was: two of three in cohort 1, three of three in cohort 1a, 16 of 30 in cohort 2, and 18 of 18 in cohort 3. Dose-limiting toxicity (DLT) consisted of elevation of both total and direct bilirubin ≥ 1.5x baseline in three patients (cohort 1: one of five patients at 50 mg; cohort 2: two of six patients at 100 mg). In cohort 2, one of seven patients had DLT at 75 mg. No DLT was encountered in cohort 3 with 12 patients at 150 mg. Apparent oral clearance (mean ± standard deviation) was cohort dependent as follows: 1.9 ± 0.2 L/h in cohort 1; 3.7 ± 4.7 L/h in cohort 1a; 2.4 ± 1.1 L/h in cohort 2; and 4.5 ± 2.7 L/h in cohort 3 (Kruskal-Wallis, P < .017). Conclusion: Patients with renal dysfunction tolerate 150 mg of erlotinib daily and seem to have an erlotinib clearance similar to patients without organ dysfunction. Patients with hepatic dysfunction should be treated at a reduced dose (ie, 75 mg daily) consistent with their reduced clearance.

Original languageEnglish (US)
Pages (from-to)3055-3060
Number of pages6
JournalJournal of Clinical Oncology
Volume25
Issue number21
DOIs
StatePublished - Jul 20 2007

Fingerprint

Pharmacokinetics
Kidney
Liver
Neoplasms
Erlotinib Hydrochloride
Bilirubin
Albumins
Creatinine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Miller, A. A., Murry, D. J., Owzar, K., Hollis, D. R., Lewis, L. D., Kindler, H. L., ... Ratain, M. J. (2007). Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101. Journal of Clinical Oncology, 25(21), 3055-3060. https://doi.org/10.1200/JCO.2007.11.6210
Miller, Antonius A. ; Murry, Daryl J. ; Owzar, Kouros ; Hollis, Donna R. ; Lewis, Lionel D. ; Kindler, Hedy L. ; Marshall, John L. ; Villalona-Calero, Miguel A. ; Edelman, Martin J. ; Hohl, Raymond J. ; Lichtman, Stuart M. ; Ratain, Mark J. / Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction : CALGB 60101. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 21. pp. 3055-3060.
@article{05bafa7a542e4541acafa39271e65b9e,
title = "Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101",
abstract = "Purpose: We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction. Patients and Methods: Patients were assigned to one of three cohorts: cohort 1, AST ≥ 3x upper limit of normal; cohort 2, direct bilirubin of 1 to 7 mg/dL; and cohort 3, creatinine of 1.6 to 5.0 mg/dL. Cohort 1a was amended for albumin less than 2.5 g/dL. Erlotinib was administered orally daily to groups of at least three assessable patients in escalating doses of 50, 75, 100, and 150 mg, starting with 50 mg in hepatic dysfunction patients and 75 mg in renal dysfunction patients. Results: Between December 2001 and May 2005, 55 patients were accrued. The distribution of assessable patients was: two of three in cohort 1, three of three in cohort 1a, 16 of 30 in cohort 2, and 18 of 18 in cohort 3. Dose-limiting toxicity (DLT) consisted of elevation of both total and direct bilirubin ≥ 1.5x baseline in three patients (cohort 1: one of five patients at 50 mg; cohort 2: two of six patients at 100 mg). In cohort 2, one of seven patients had DLT at 75 mg. No DLT was encountered in cohort 3 with 12 patients at 150 mg. Apparent oral clearance (mean ± standard deviation) was cohort dependent as follows: 1.9 ± 0.2 L/h in cohort 1; 3.7 ± 4.7 L/h in cohort 1a; 2.4 ± 1.1 L/h in cohort 2; and 4.5 ± 2.7 L/h in cohort 3 (Kruskal-Wallis, P < .017). Conclusion: Patients with renal dysfunction tolerate 150 mg of erlotinib daily and seem to have an erlotinib clearance similar to patients without organ dysfunction. Patients with hepatic dysfunction should be treated at a reduced dose (ie, 75 mg daily) consistent with their reduced clearance.",
author = "Miller, {Antonius A.} and Murry, {Daryl J.} and Kouros Owzar and Hollis, {Donna R.} and Lewis, {Lionel D.} and Kindler, {Hedy L.} and Marshall, {John L.} and Villalona-Calero, {Miguel A.} and Edelman, {Martin J.} and Hohl, {Raymond J.} and Lichtman, {Stuart M.} and Ratain, {Mark J.}",
year = "2007",
month = "7",
day = "20",
doi = "10.1200/JCO.2007.11.6210",
language = "English (US)",
volume = "25",
pages = "3055--3060",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "21",

}

Miller, AA, Murry, DJ, Owzar, K, Hollis, DR, Lewis, LD, Kindler, HL, Marshall, JL, Villalona-Calero, MA, Edelman, MJ, Hohl, RJ, Lichtman, SM & Ratain, MJ 2007, 'Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101', Journal of Clinical Oncology, vol. 25, no. 21, pp. 3055-3060. https://doi.org/10.1200/JCO.2007.11.6210

Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction : CALGB 60101. / Miller, Antonius A.; Murry, Daryl J.; Owzar, Kouros; Hollis, Donna R.; Lewis, Lionel D.; Kindler, Hedy L.; Marshall, John L.; Villalona-Calero, Miguel A.; Edelman, Martin J.; Hohl, Raymond J.; Lichtman, Stuart M.; Ratain, Mark J.

In: Journal of Clinical Oncology, Vol. 25, No. 21, 20.07.2007, p. 3055-3060.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction

T2 - CALGB 60101

AU - Miller, Antonius A.

AU - Murry, Daryl J.

AU - Owzar, Kouros

AU - Hollis, Donna R.

AU - Lewis, Lionel D.

AU - Kindler, Hedy L.

AU - Marshall, John L.

AU - Villalona-Calero, Miguel A.

AU - Edelman, Martin J.

AU - Hohl, Raymond J.

AU - Lichtman, Stuart M.

AU - Ratain, Mark J.

PY - 2007/7/20

Y1 - 2007/7/20

N2 - Purpose: We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction. Patients and Methods: Patients were assigned to one of three cohorts: cohort 1, AST ≥ 3x upper limit of normal; cohort 2, direct bilirubin of 1 to 7 mg/dL; and cohort 3, creatinine of 1.6 to 5.0 mg/dL. Cohort 1a was amended for albumin less than 2.5 g/dL. Erlotinib was administered orally daily to groups of at least three assessable patients in escalating doses of 50, 75, 100, and 150 mg, starting with 50 mg in hepatic dysfunction patients and 75 mg in renal dysfunction patients. Results: Between December 2001 and May 2005, 55 patients were accrued. The distribution of assessable patients was: two of three in cohort 1, three of three in cohort 1a, 16 of 30 in cohort 2, and 18 of 18 in cohort 3. Dose-limiting toxicity (DLT) consisted of elevation of both total and direct bilirubin ≥ 1.5x baseline in three patients (cohort 1: one of five patients at 50 mg; cohort 2: two of six patients at 100 mg). In cohort 2, one of seven patients had DLT at 75 mg. No DLT was encountered in cohort 3 with 12 patients at 150 mg. Apparent oral clearance (mean ± standard deviation) was cohort dependent as follows: 1.9 ± 0.2 L/h in cohort 1; 3.7 ± 4.7 L/h in cohort 1a; 2.4 ± 1.1 L/h in cohort 2; and 4.5 ± 2.7 L/h in cohort 3 (Kruskal-Wallis, P < .017). Conclusion: Patients with renal dysfunction tolerate 150 mg of erlotinib daily and seem to have an erlotinib clearance similar to patients without organ dysfunction. Patients with hepatic dysfunction should be treated at a reduced dose (ie, 75 mg daily) consistent with their reduced clearance.

AB - Purpose: We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction. Patients and Methods: Patients were assigned to one of three cohorts: cohort 1, AST ≥ 3x upper limit of normal; cohort 2, direct bilirubin of 1 to 7 mg/dL; and cohort 3, creatinine of 1.6 to 5.0 mg/dL. Cohort 1a was amended for albumin less than 2.5 g/dL. Erlotinib was administered orally daily to groups of at least three assessable patients in escalating doses of 50, 75, 100, and 150 mg, starting with 50 mg in hepatic dysfunction patients and 75 mg in renal dysfunction patients. Results: Between December 2001 and May 2005, 55 patients were accrued. The distribution of assessable patients was: two of three in cohort 1, three of three in cohort 1a, 16 of 30 in cohort 2, and 18 of 18 in cohort 3. Dose-limiting toxicity (DLT) consisted of elevation of both total and direct bilirubin ≥ 1.5x baseline in three patients (cohort 1: one of five patients at 50 mg; cohort 2: two of six patients at 100 mg). In cohort 2, one of seven patients had DLT at 75 mg. No DLT was encountered in cohort 3 with 12 patients at 150 mg. Apparent oral clearance (mean ± standard deviation) was cohort dependent as follows: 1.9 ± 0.2 L/h in cohort 1; 3.7 ± 4.7 L/h in cohort 1a; 2.4 ± 1.1 L/h in cohort 2; and 4.5 ± 2.7 L/h in cohort 3 (Kruskal-Wallis, P < .017). Conclusion: Patients with renal dysfunction tolerate 150 mg of erlotinib daily and seem to have an erlotinib clearance similar to patients without organ dysfunction. Patients with hepatic dysfunction should be treated at a reduced dose (ie, 75 mg daily) consistent with their reduced clearance.

UR - http://www.scopus.com/inward/record.url?scp=34547701893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547701893&partnerID=8YFLogxK

U2 - 10.1200/JCO.2007.11.6210

DO - 10.1200/JCO.2007.11.6210

M3 - Article

C2 - 17634483

AN - SCOPUS:34547701893

VL - 25

SP - 3055

EP - 3060

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 21

ER -