Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer

I. Craig Henderson, Donald A. Berry, George D. Demetri, Constance T. Cirrincione, Lori J. Goldstein, Silvana Martino, James N. Ingle, M. Robert Cooper, Daniel F. Hayes, Katherine H. Tkaczuk, Gini Fleming, James F. Holland, David B. Duggan, John T. Carpenter, Emil Frei, Richard L. Schilsky, William C. Wood, Hyman B. Muss, Larry Norton

Research output: Contribution to journalArticle

1034 Citations (Scopus)

Abstract

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor-positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

Original languageEnglish (US)
Pages (from-to)976-983
Number of pages8
JournalJournal of Clinical Oncology
Volume21
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

Fingerprint

Adjuvant Chemotherapy
Paclitaxel
Doxorubicin
Breast Neoplasms
Disease-Free Survival
Tamoxifen
Estrogen Receptors
Confidence Intervals
Recurrence
Neoplasms
Survival
Cyclophosphamide
Lymph Nodes
Hormones
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. / Henderson, I. Craig; Berry, Donald A.; Demetri, George D.; Cirrincione, Constance T.; Goldstein, Lori J.; Martino, Silvana; Ingle, James N.; Cooper, M. Robert; Hayes, Daniel F.; Tkaczuk, Katherine H.; Fleming, Gini; Holland, James F.; Duggan, David B.; Carpenter, John T.; Frei, Emil; Schilsky, Richard L.; Wood, William C.; Muss, Hyman B.; Norton, Larry.

In: Journal of Clinical Oncology, Vol. 21, No. 6, 15.03.2003, p. 976-983.

Research output: Contribution to journalArticle

Henderson, IC, Berry, DA, Demetri, GD, Cirrincione, CT, Goldstein, LJ, Martino, S, Ingle, JN, Cooper, MR, Hayes, DF, Tkaczuk, KH, Fleming, G, Holland, JF, Duggan, DB, Carpenter, JT, Frei, E, Schilsky, RL, Wood, WC, Muss, HB & Norton, L 2003, 'Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer', Journal of Clinical Oncology, vol. 21, no. 6, pp. 976-983. https://doi.org/10.1200/JCO.2003.02.063
Henderson, I. Craig ; Berry, Donald A. ; Demetri, George D. ; Cirrincione, Constance T. ; Goldstein, Lori J. ; Martino, Silvana ; Ingle, James N. ; Cooper, M. Robert ; Hayes, Daniel F. ; Tkaczuk, Katherine H. ; Fleming, Gini ; Holland, James F. ; Duggan, David B. ; Carpenter, John T. ; Frei, Emil ; Schilsky, Richard L. ; Wood, William C. ; Muss, Hyman B. ; Norton, Larry. / Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 6. pp. 976-983.
@article{93e4d2a61cfd400b8bed2bffcb29cb79,
title = "Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer",
abstract = "Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94{\%} of patients with hormone receptor-positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69{\%}, 66{\%}, and 67{\%} for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17{\%} for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18{\%} for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65{\%} (± 1) and 70{\%} (± 1), and overall survival was 77{\%} (± 1) and 80{\%} (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95{\%} confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95{\%} confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.",
author = "Henderson, {I. Craig} and Berry, {Donald A.} and Demetri, {George D.} and Cirrincione, {Constance T.} and Goldstein, {Lori J.} and Silvana Martino and Ingle, {James N.} and Cooper, {M. Robert} and Hayes, {Daniel F.} and Tkaczuk, {Katherine H.} and Gini Fleming and Holland, {James F.} and Duggan, {David B.} and Carpenter, {John T.} and Emil Frei and Schilsky, {Richard L.} and Wood, {William C.} and Muss, {Hyman B.} and Larry Norton",
year = "2003",
month = "3",
day = "15",
doi = "10.1200/JCO.2003.02.063",
language = "English (US)",
volume = "21",
pages = "976--983",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer

AU - Henderson, I. Craig

AU - Berry, Donald A.

AU - Demetri, George D.

AU - Cirrincione, Constance T.

AU - Goldstein, Lori J.

AU - Martino, Silvana

AU - Ingle, James N.

AU - Cooper, M. Robert

AU - Hayes, Daniel F.

AU - Tkaczuk, Katherine H.

AU - Fleming, Gini

AU - Holland, James F.

AU - Duggan, David B.

AU - Carpenter, John T.

AU - Frei, Emil

AU - Schilsky, Richard L.

AU - Wood, William C.

AU - Muss, Hyman B.

AU - Norton, Larry

PY - 2003/3/15

Y1 - 2003/3/15

N2 - Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor-positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

AB - Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor-positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=0037445132&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037445132&partnerID=8YFLogxK

U2 - 10.1200/JCO.2003.02.063

DO - 10.1200/JCO.2003.02.063

M3 - Article

C2 - 12637460

AN - SCOPUS:0037445132

VL - 21

SP - 976

EP - 983

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -