Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741

Marc L. Citron, Donald A. Berry, Constance Cirrincione, Clifford Hudis, Eric P. Winer, William J. Gradishar, Nancy E. Davidson, Silvana Martino, Robert Livingston, James N. Ingle, Edith A. Perez, John Carpenter, David Hurd, James F. Holland, Barbara L. Smith, Carolyn I. Sartor, Eleanor H. Leung, Jeffrey Abrams, Richard L. Schilsky, Hyman B. MussLarry Norton

Research output: Contribution to journalArticle

1182 Citations (Scopus)

Abstract

Purpose: Using a 2 × 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A × 4 (doses) → T × 4 → C × 4 with doses every 3 weeks, (II) sequential A × 4 → T × 4 C × 4 every 2 weeks with filgrastim, (III) concurrent AC × 4 → T 4 every 3 weeks, or (IV) concurrent AC × 4 → T × 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.

Original languageEnglish (US)
Pages (from-to)1431-1439
Number of pages9
JournalJournal of Clinical Oncology
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2003
Externally publishedYes

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Combination Drug Therapy
Cyclophosphamide
Leukemia
Breast Neoplasms
Survival
Paclitaxel
Doxorubicin
Neoplasms
Odds Ratio
Drug Therapy
Therapeutics
Adjuvant Chemotherapy
Neutropenia
Treatment Failure
Appointments and Schedules
Recurrence
Filgrastim

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer : First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. / Citron, Marc L.; Berry, Donald A.; Cirrincione, Constance; Hudis, Clifford; Winer, Eric P.; Gradishar, William J.; Davidson, Nancy E.; Martino, Silvana; Livingston, Robert; Ingle, James N.; Perez, Edith A.; Carpenter, John; Hurd, David; Holland, James F.; Smith, Barbara L.; Sartor, Carolyn I.; Leung, Eleanor H.; Abrams, Jeffrey; Schilsky, Richard L.; Muss, Hyman B.; Norton, Larry.

In: Journal of Clinical Oncology, Vol. 21, No. 8, 15.04.2003, p. 1431-1439.

Research output: Contribution to journalArticle

Citron, ML, Berry, DA, Cirrincione, C, Hudis, C, Winer, EP, Gradishar, WJ, Davidson, NE, Martino, S, Livingston, R, Ingle, JN, Perez, EA, Carpenter, J, Hurd, D, Holland, JF, Smith, BL, Sartor, CI, Leung, EH, Abrams, J, Schilsky, RL, Muss, HB & Norton, L 2003, 'Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741', Journal of Clinical Oncology, vol. 21, no. 8, pp. 1431-1439. https://doi.org/10.1200/JCO.2003.09.081
Citron, Marc L. ; Berry, Donald A. ; Cirrincione, Constance ; Hudis, Clifford ; Winer, Eric P. ; Gradishar, William J. ; Davidson, Nancy E. ; Martino, Silvana ; Livingston, Robert ; Ingle, James N. ; Perez, Edith A. ; Carpenter, John ; Hurd, David ; Holland, James F. ; Smith, Barbara L. ; Sartor, Carolyn I. ; Leung, Eleanor H. ; Abrams, Jeffrey ; Schilsky, Richard L. ; Muss, Hyman B. ; Norton, Larry. / Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer : First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 8. pp. 1431-1439.
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abstract = "Purpose: Using a 2 × 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A × 4 (doses) → T × 4 → C × 4 with doses every 3 weeks, (II) sequential A × 4 → T × 4 C × 4 every 2 weeks with filgrastim, (III) concurrent AC × 4 → T 4 every 3 weeks, or (IV) concurrent AC × 4 → T × 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82{\%} for the dose-dense regimens and 75{\%} for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.",
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T1 - Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer

T2 - First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741

AU - Citron, Marc L.

AU - Berry, Donald A.

AU - Cirrincione, Constance

AU - Hudis, Clifford

AU - Winer, Eric P.

AU - Gradishar, William J.

AU - Davidson, Nancy E.

AU - Martino, Silvana

AU - Livingston, Robert

AU - Ingle, James N.

AU - Perez, Edith A.

AU - Carpenter, John

AU - Hurd, David

AU - Holland, James F.

AU - Smith, Barbara L.

AU - Sartor, Carolyn I.

AU - Leung, Eleanor H.

AU - Abrams, Jeffrey

AU - Schilsky, Richard L.

AU - Muss, Hyman B.

AU - Norton, Larry

PY - 2003/4/15

Y1 - 2003/4/15

N2 - Purpose: Using a 2 × 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A × 4 (doses) → T × 4 → C × 4 with doses every 3 weeks, (II) sequential A × 4 → T × 4 C × 4 every 2 weeks with filgrastim, (III) concurrent AC × 4 → T 4 every 3 weeks, or (IV) concurrent AC × 4 → T × 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.

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