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, Ramesk 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

436 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 - 2008
Externally publishedYes

Fingerprint

oxaliplatin
Colorectal Neoplasms
Safety
Therapeutics
Leucovorin
Fluorouracil
Survival
Bevacizumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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, Ramesk 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, 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, Ramesk 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{9051426285314cdea1f9ea26ad1c0f67,
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, {Ramesk 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",
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, Ramesk 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

Y1 - 2008

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

C2 - 18640933

AN - SCOPUS:49049105525

VL - 26

SP - 3523

EP - 3529

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 21

ER -