Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma

Carlos H. Barrios, David Hernandez-Barajas, Michael P. Brown, Se Hoon Lee, Luis Fein, Jin Hwang Liu, Subramanian Hariharan, Bridget A. Martell, Jinyu Yuan, Akintunde Bello, Zhixiao Wang, Rajiv Mundayat, Sun Young Rha

Research output: Contribution to journalArticle

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Abstract

Background: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment. Methods: One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO). Results: Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. Conclusions: Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.

Original languageEnglish
Pages (from-to)1252-1259
Number of pages8
JournalCancer
Volume118
Issue number5
DOIs
Publication statusPublished - 2012 Mar 1

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Renal Cell Carcinoma
Hand-Foot Syndrome
Cell- and Tissue-Based Therapy
Safety
Disease-Free Survival
Diarrhea
Therapeutics
Pharmacokinetics
Neutropenia
Fatigue
sunitinib
Appointments and Schedules
Biomarkers
Survival
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Barrios, Carlos H. ; Hernandez-Barajas, David ; Brown, Michael P. ; Lee, Se Hoon ; Fein, Luis ; Liu, Jin Hwang ; Hariharan, Subramanian ; Martell, Bridget A. ; Yuan, Jinyu ; Bello, Akintunde ; Wang, Zhixiao ; Mundayat, Rajiv ; Rha, Sun Young. / Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma. In: Cancer. 2012 ; Vol. 118, No. 5. pp. 1252-1259.
@article{6ce3062ffdec46919c2bc8f05ec2aa25,
title = "Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma",
abstract = "Background: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment. Methods: One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO). Results: Objective response rate (ORR) was 35.3{\%}; median response duration was 10.4 months; 36{\%} of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8{\%}. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50{\%}) and hand-foot syndrome (43{\%}); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13{\%}), neutropenia (11{\%}), and diarrhea (9{\%}). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. Conclusions: Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.",
author = "Barrios, {Carlos H.} and David Hernandez-Barajas and Brown, {Michael P.} and Lee, {Se Hoon} and Luis Fein and Liu, {Jin Hwang} and Subramanian Hariharan and Martell, {Bridget A.} and Jinyu Yuan and Akintunde Bello and Zhixiao Wang and Rajiv Mundayat and Rha, {Sun Young}",
year = "2012",
month = "3",
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doi = "10.1002/cncr.26440",
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Barrios, CH, Hernandez-Barajas, D, Brown, MP, Lee, SH, Fein, L, Liu, JH, Hariharan, S, Martell, BA, Yuan, J, Bello, A, Wang, Z, Mundayat, R & Rha, SY 2012, 'Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma', Cancer, vol. 118, no. 5, pp. 1252-1259. https://doi.org/10.1002/cncr.26440

Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma. / Barrios, Carlos H.; Hernandez-Barajas, David; Brown, Michael P.; Lee, Se Hoon; Fein, Luis; Liu, Jin Hwang; Hariharan, Subramanian; Martell, Bridget A.; Yuan, Jinyu; Bello, Akintunde; Wang, Zhixiao; Mundayat, Rajiv; Rha, Sun Young.

In: Cancer, Vol. 118, No. 5, 01.03.2012, p. 1252-1259.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma

AU - Barrios, Carlos H.

AU - Hernandez-Barajas, David

AU - Brown, Michael P.

AU - Lee, Se Hoon

AU - Fein, Luis

AU - Liu, Jin Hwang

AU - Hariharan, Subramanian

AU - Martell, Bridget A.

AU - Yuan, Jinyu

AU - Bello, Akintunde

AU - Wang, Zhixiao

AU - Mundayat, Rajiv

AU - Rha, Sun Young

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Background: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment. Methods: One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO). Results: Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. Conclusions: Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.

AB - Background: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment. Methods: One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO). Results: Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. Conclusions: Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.

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DO - 10.1002/cncr.26440

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