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

Publication ,  Journal Article
Miller, AA; Murry, DJ; Owzar, K; Hollis, DR; Lewis, LD; Kindler, HL; Marshall, JL; Villalona-Calero, MA; Edelman, MJ; Hohl, RJ; Lichtman, SM ...
Published in: J Clin Oncol
July 20, 2007

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 > or = 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.

Duke Scholars

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

July 20, 2007

Volume

25

Issue

21

Start / End Page

3055 / 3060

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Survival Analysis
  • Risk Assessment
  • Quinazolines
  • Probability
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Staging
  • Middle Aged
  • Maximum Tolerated Dose
 

Citation

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MLA
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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. J Clin Oncol, 25(21), 3055–3060. https://doi.org/10.1200/JCO.2007.11.6210
Miller, Antonius A., Daryl J. Murry, Kouros Owzar, Donna R. Hollis, Lionel D. Lewis, Hedy L. Kindler, John L. Marshall, et al. “Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101.J Clin Oncol 25, no. 21 (July 20, 2007): 3055–60. https://doi.org/10.1200/JCO.2007.11.6210.
Miller AA, Murry DJ, Owzar K, Hollis DR, Lewis LD, Kindler HL, et al. Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101. J Clin Oncol. 2007 Jul 20;25(21):3055–60.
Miller, Antonius A., et al. “Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101.J Clin Oncol, vol. 25, no. 21, July 2007, pp. 3055–60. Pubmed, doi:10.1200/JCO.2007.11.6210.
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. Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101. J Clin Oncol. 2007 Jul 20;25(21):3055–3060.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

July 20, 2007

Volume

25

Issue

21

Start / End Page

3055 / 3060

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Survival Analysis
  • Risk Assessment
  • Quinazolines
  • Probability
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Staging
  • Middle Aged
  • Maximum Tolerated Dose