Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer

Results of the TREE study

Howard S. Hochster, Lowell L. Hart, Ramesh K. Ramanathan, Barrett H. Childs, John D. Hainsworth, Allen L. Cohn, Lucas Wong, Louis Fehrenbacher, Yousif Abubakr, M. Wasif Saif, Lee Schwartzberg, Eric Hedrick

Research output: Contribution to journalArticle

429 Citations (Scopus)

Abstract

Purpose: To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC). Patients and Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2). Results: A total of 150 and 223 patients were randomly assigned in the TREE-1 and TREE-2 cohorts, respectively. Incidence of grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59%, 36%, and 67% for mFOLFOX6, bFOL, and CapeOx, respectively, (TREE-1) and 59%, 51%, and 56% for the corresponding treatments plus bevacizumab (TREE-2; primary end point). CapeOx toxicity in TREE-1 included grade 3/4 diarrhea (31%) and dehydration (27%); capecitabine dose reduction to 1,700 mg/m2/d in TREE-2 resulted in improved tolerance. Overall response rates were 41%, 20%, and 27% (TREE-1) and 52%, 39%, and 46% (TREE-2); median overall survival (OS) was 19.2, 17.9, and 17.2 months (TREE-1) and 26.1, 20.4, and 24.6 months (TREE-2). For all treated patients, median OS was 18.2 months (95% CI, 14.5 to 21.6; TREE-1) and 23.7 months (95% CI, 21.3 to 26.8; TREE-2). Conclusion: The addition of bevacizumab to oxaliplatin and fluoropyrimidine regimens is well tolerated as first-line treatment of mCRC and does not markedly change overall toxicity. CapeOx tolerability and efficacy is improved with reduced-dose capecitabine. First-line oxaliplatin and fluoropyrimidine-based therapy plus bevacizumab resulted in a median OS of approximately 2 years.

Original languageEnglish (US)
Pages (from-to)3523-3529
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number21
DOIs
StatePublished - Sep 15 2008

Fingerprint

oxaliplatin
Colorectal Neoplasms
Safety
Therapeutics
Leucovorin
Fluorouracil
Survival
Bevacizumab

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer : Results of the TREE study. / Hochster, Howard S.; Hart, Lowell L.; Ramanathan, Ramesh K.; Childs, Barrett H.; Hainsworth, John D.; Cohn, Allen L.; Wong, Lucas; Fehrenbacher, Louis; Abubakr, Yousif; Saif, M. Wasif; Schwartzberg, Lee; Hedrick, Eric.

In: Journal of Clinical Oncology, Vol. 26, No. 21, 15.09.2008, p. 3523-3529.

Research output: Contribution to journalArticle

Hochster, HS, Hart, LL, Ramanathan, RK, Childs, BH, Hainsworth, JD, Cohn, AL, Wong, L, Fehrenbacher, L, Abubakr, Y, Saif, MW, Schwartzberg, L & Hedrick, E 2008, 'Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: Results of the TREE study', Journal of Clinical Oncology, vol. 26, no. 21, pp. 3523-3529. https://doi.org/10.1200/JCO.2007.15.4138
Hochster, Howard S. ; Hart, Lowell L. ; Ramanathan, Ramesh K. ; Childs, Barrett H. ; Hainsworth, John D. ; Cohn, Allen L. ; Wong, Lucas ; Fehrenbacher, Louis ; Abubakr, Yousif ; Saif, M. Wasif ; Schwartzberg, Lee ; Hedrick, Eric. / Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer : Results of the TREE study. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 21. pp. 3523-3529.
@article{2b125b86576d439e957e25b4fcdafa9b,
title = "Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: Results of the TREE study",
abstract = "Purpose: To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC). Patients and Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2). Results: A total of 150 and 223 patients were randomly assigned in the TREE-1 and TREE-2 cohorts, respectively. Incidence of grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59{\%}, 36{\%}, and 67{\%} for mFOLFOX6, bFOL, and CapeOx, respectively, (TREE-1) and 59{\%}, 51{\%}, and 56{\%} for the corresponding treatments plus bevacizumab (TREE-2; primary end point). CapeOx toxicity in TREE-1 included grade 3/4 diarrhea (31{\%}) and dehydration (27{\%}); capecitabine dose reduction to 1,700 mg/m2/d in TREE-2 resulted in improved tolerance. Overall response rates were 41{\%}, 20{\%}, and 27{\%} (TREE-1) and 52{\%}, 39{\%}, and 46{\%} (TREE-2); median overall survival (OS) was 19.2, 17.9, and 17.2 months (TREE-1) and 26.1, 20.4, and 24.6 months (TREE-2). For all treated patients, median OS was 18.2 months (95{\%} CI, 14.5 to 21.6; TREE-1) and 23.7 months (95{\%} CI, 21.3 to 26.8; TREE-2). Conclusion: The addition of bevacizumab to oxaliplatin and fluoropyrimidine regimens is well tolerated as first-line treatment of mCRC and does not markedly change overall toxicity. CapeOx tolerability and efficacy is improved with reduced-dose capecitabine. First-line oxaliplatin and fluoropyrimidine-based therapy plus bevacizumab resulted in a median OS of approximately 2 years.",
author = "Hochster, {Howard S.} and Hart, {Lowell L.} and Ramanathan, {Ramesh K.} and Childs, {Barrett H.} and Hainsworth, {John D.} and Cohn, {Allen L.} and Lucas Wong and Louis Fehrenbacher and Yousif Abubakr and Saif, {M. Wasif} and Lee Schwartzberg and Eric Hedrick",
year = "2008",
month = "9",
day = "15",
doi = "10.1200/JCO.2007.15.4138",
language = "English (US)",
volume = "26",
pages = "3523--3529",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "21",

}

TY - JOUR

T1 - Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer

T2 - Results of the TREE study

AU - Hochster, Howard S.

AU - Hart, Lowell L.

AU - Ramanathan, Ramesh K.

AU - Childs, Barrett H.

AU - Hainsworth, John D.

AU - Cohn, Allen L.

AU - Wong, Lucas

AU - Fehrenbacher, Louis

AU - Abubakr, Yousif

AU - Saif, M. Wasif

AU - Schwartzberg, Lee

AU - Hedrick, Eric

PY - 2008/9/15

Y1 - 2008/9/15

N2 - Purpose: To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC). Patients and Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2). Results: A total of 150 and 223 patients were randomly assigned in the TREE-1 and TREE-2 cohorts, respectively. Incidence of grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59%, 36%, and 67% for mFOLFOX6, bFOL, and CapeOx, respectively, (TREE-1) and 59%, 51%, and 56% for the corresponding treatments plus bevacizumab (TREE-2; primary end point). CapeOx toxicity in TREE-1 included grade 3/4 diarrhea (31%) and dehydration (27%); capecitabine dose reduction to 1,700 mg/m2/d in TREE-2 resulted in improved tolerance. Overall response rates were 41%, 20%, and 27% (TREE-1) and 52%, 39%, and 46% (TREE-2); median overall survival (OS) was 19.2, 17.9, and 17.2 months (TREE-1) and 26.1, 20.4, and 24.6 months (TREE-2). For all treated patients, median OS was 18.2 months (95% CI, 14.5 to 21.6; TREE-1) and 23.7 months (95% CI, 21.3 to 26.8; TREE-2). Conclusion: The addition of bevacizumab to oxaliplatin and fluoropyrimidine regimens is well tolerated as first-line treatment of mCRC and does not markedly change overall toxicity. CapeOx tolerability and efficacy is improved with reduced-dose capecitabine. First-line oxaliplatin and fluoropyrimidine-based therapy plus bevacizumab resulted in a median OS of approximately 2 years.

AB - Purpose: To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC). Patients and Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2). Results: A total of 150 and 223 patients were randomly assigned in the TREE-1 and TREE-2 cohorts, respectively. Incidence of grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59%, 36%, and 67% for mFOLFOX6, bFOL, and CapeOx, respectively, (TREE-1) and 59%, 51%, and 56% for the corresponding treatments plus bevacizumab (TREE-2; primary end point). CapeOx toxicity in TREE-1 included grade 3/4 diarrhea (31%) and dehydration (27%); capecitabine dose reduction to 1,700 mg/m2/d in TREE-2 resulted in improved tolerance. Overall response rates were 41%, 20%, and 27% (TREE-1) and 52%, 39%, and 46% (TREE-2); median overall survival (OS) was 19.2, 17.9, and 17.2 months (TREE-1) and 26.1, 20.4, and 24.6 months (TREE-2). For all treated patients, median OS was 18.2 months (95% CI, 14.5 to 21.6; TREE-1) and 23.7 months (95% CI, 21.3 to 26.8; TREE-2). Conclusion: The addition of bevacizumab to oxaliplatin and fluoropyrimidine regimens is well tolerated as first-line treatment of mCRC and does not markedly change overall toxicity. CapeOx tolerability and efficacy is improved with reduced-dose capecitabine. First-line oxaliplatin and fluoropyrimidine-based therapy plus bevacizumab resulted in a median OS of approximately 2 years.

UR - http://www.scopus.com/inward/record.url?scp=49049105525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49049105525&partnerID=8YFLogxK

U2 - 10.1200/JCO.2007.15.4138

DO - 10.1200/JCO.2007.15.4138

M3 - Article

VL - 26

SP - 3523

EP - 3529

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 21

ER -