Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer

Results of a randomized, multicenter, phase III trial

Jean Marc Nabholtz, Carla Falkson, Daniel Campos, J. Szántó, Miguel Martin, Stephen Chan, Tadeuz Pienkowski, Jerzy Zaluski, T. Pintér, Maciej Krzakowski, Daniel Vorobiof, Robert Leonard, Ian Kennedy, Nacer Azli, Michael Murawsky, Alessandro Riva, Pierre Pouillart

Research output: Contribution to journalArticle

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Abstract

Purpose: This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC). Patients and Methods: Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m 2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles. Results: Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank p = .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P = .009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P <.001; 8% v 2%, P = .01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%). Conclusion: AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.

Original languageEnglish
Pages (from-to)968-975
Number of pages8
JournalJournal of Clinical Oncology
Volume21
Issue number6
DOIs
Publication statusPublished - Mar 15 2003

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docetaxel
Doxorubicin
Cyclophosphamide
Breast Neoplasms
Drug Therapy
Treatment Failure
Febrile Neutropenia
Survival
Adjuvant Chemotherapy
Neutropenia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer : Results of a randomized, multicenter, phase III trial. / Nabholtz, Jean Marc; Falkson, Carla; Campos, Daniel; Szántó, J.; Martin, Miguel; Chan, Stephen; Pienkowski, Tadeuz; Zaluski, Jerzy; Pintér, T.; Krzakowski, Maciej; Vorobiof, Daniel; Leonard, Robert; Kennedy, Ian; Azli, Nacer; Murawsky, Michael; Riva, Alessandro; Pouillart, Pierre.

In: Journal of Clinical Oncology, Vol. 21, No. 6, 15.03.2003, p. 968-975.

Research output: Contribution to journalArticle

Nabholtz, JM, Falkson, C, Campos, D, Szántó, J, Martin, M, Chan, S, Pienkowski, T, Zaluski, J, Pintér, T, Krzakowski, M, Vorobiof, D, Leonard, R, Kennedy, I, Azli, N, Murawsky, M, Riva, A & Pouillart, P 2003, 'Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: Results of a randomized, multicenter, phase III trial', Journal of Clinical Oncology, vol. 21, no. 6, pp. 968-975. https://doi.org/10.1200/JCO.2003.04.040
Nabholtz, Jean Marc ; Falkson, Carla ; Campos, Daniel ; Szántó, J. ; Martin, Miguel ; Chan, Stephen ; Pienkowski, Tadeuz ; Zaluski, Jerzy ; Pintér, T. ; Krzakowski, Maciej ; Vorobiof, Daniel ; Leonard, Robert ; Kennedy, Ian ; Azli, Nacer ; Murawsky, Michael ; Riva, Alessandro ; Pouillart, Pierre. / Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer : Results of a randomized, multicenter, phase III trial. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 6. pp. 968-975.
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abstract = "Purpose: This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC). Patients and Methods: Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m 2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles. Results: Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank p = .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048). The overall response rate (ORR) was significantly greater for patients taking AT (59{\%}, with 10{\%} complete response [CR], 49{\%} partial response [PR]) than for those taking AC (47{\%}, with 7{\%} CR, 39{\%} PR) (P = .009). The ORR was also higher with AT in patients with visceral involvement (58{\%} v 41{\%}; liver, 62{\%} v 42{\%}; lung, 58{\%} v 35{\%}), three or more organs involved (59{\%} v 40{\%}), or prior adjuvant CT (53{\%} v41{\%}). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33{\%} v 10{\%}, P <.001; 8{\%} v 2{\%}, P = .01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3{\%}; AC, 4{\%}). Conclusion: AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.",
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T1 - Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer

T2 - Results of a randomized, multicenter, phase III trial

AU - Nabholtz, Jean Marc

AU - Falkson, Carla

AU - Campos, Daniel

AU - Szántó, J.

AU - Martin, Miguel

AU - Chan, Stephen

AU - Pienkowski, Tadeuz

AU - Zaluski, Jerzy

AU - Pintér, T.

AU - Krzakowski, Maciej

AU - Vorobiof, Daniel

AU - Leonard, Robert

AU - Kennedy, Ian

AU - Azli, Nacer

AU - Murawsky, Michael

AU - Riva, Alessandro

AU - Pouillart, Pierre

PY - 2003/3/15

Y1 - 2003/3/15

N2 - Purpose: This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC). Patients and Methods: Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m 2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles. Results: Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank p = .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P = .009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P <.001; 8% v 2%, P = .01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%). Conclusion: AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.

AB - Purpose: This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC). Patients and Methods: Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m 2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles. Results: Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank p = .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P = .009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P <.001; 8% v 2%, P = .01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%). Conclusion: AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.

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