A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer

J. W. Kugler, E. A. Perez, L. Geeraerts, J. M. Lafky, J. N. Ingle, V. J. Suman, A. A. Adjei, A. T. Baron, A. K. Hatfield, Nita Jane Maihle, J. C. Michalak, S. A. Kuross

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease. Patients and methods: Thirty-three patients were randomized to either docetaxel (100 mg/m2) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m2) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately. Results: Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35% [95% confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15% to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment. Conclusions: Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.

Original languageEnglish (US)
Pages (from-to)1225-1235
Number of pages11
JournalAnnals of Oncology
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2002

Fingerprint

docetaxel
Doxorubicin
Cyclophosphamide
Breast Neoplasms
Serum
Therapeutics
Drug Therapy
Appointments and Schedules
Confidence Intervals

Keywords

  • Breast cancer
  • Chemotherapy
  • Docetaxel

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Kugler, J. W., Perez, E. A., Geeraerts, L., Lafky, J. M., Ingle, J. N., Suman, V. J., ... Kuross, S. A. (2002). A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer. Annals of Oncology, 13(8), 1225-1235. https://doi.org/10.1093/annonc/mdf222

A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer. / Kugler, J. W.; Perez, E. A.; Geeraerts, L.; Lafky, J. M.; Ingle, J. N.; Suman, V. J.; Adjei, A. A.; Baron, A. T.; Hatfield, A. K.; Maihle, Nita Jane; Michalak, J. C.; Kuross, S. A.

In: Annals of Oncology, Vol. 13, No. 8, 01.08.2002, p. 1225-1235.

Research output: Contribution to journalArticle

Kugler, JW, Perez, EA, Geeraerts, L, Lafky, JM, Ingle, JN, Suman, VJ, Adjei, AA, Baron, AT, Hatfield, AK, Maihle, NJ, Michalak, JC & Kuross, SA 2002, 'A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer', Annals of Oncology, vol. 13, no. 8, pp. 1225-1235. https://doi.org/10.1093/annonc/mdf222
Kugler, J. W. ; Perez, E. A. ; Geeraerts, L. ; Lafky, J. M. ; Ingle, J. N. ; Suman, V. J. ; Adjei, A. A. ; Baron, A. T. ; Hatfield, A. K. ; Maihle, Nita Jane ; Michalak, J. C. ; Kuross, S. A. / A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer. In: Annals of Oncology. 2002 ; Vol. 13, No. 8. pp. 1225-1235.
@article{a56762dc85e241ffbf9dd8c0c3c4c73f,
title = "A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer",
abstract = "Background: Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease. Patients and methods: Thirty-three patients were randomized to either docetaxel (100 mg/m2) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m2) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately. Results: Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35{\%} [95{\%} confidence interval (CI) 14{\%} to 62{\%}] with docetaxel then AC and 38{\%} (95{\%} CI 15{\%} to 65{\%}) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment. Conclusions: Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.",
keywords = "Breast cancer, Chemotherapy, Docetaxel",
author = "Kugler, {J. W.} and Perez, {E. A.} and L. Geeraerts and Lafky, {J. M.} and Ingle, {J. N.} and Suman, {V. J.} and Adjei, {A. A.} and Baron, {A. T.} and Hatfield, {A. K.} and Maihle, {Nita Jane} and Michalak, {J. C.} and Kuross, {S. A.}",
year = "2002",
month = "8",
day = "1",
doi = "10.1093/annonc/mdf222",
language = "English (US)",
volume = "13",
pages = "1225--1235",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer

AU - Kugler, J. W.

AU - Perez, E. A.

AU - Geeraerts, L.

AU - Lafky, J. M.

AU - Ingle, J. N.

AU - Suman, V. J.

AU - Adjei, A. A.

AU - Baron, A. T.

AU - Hatfield, A. K.

AU - Maihle, Nita Jane

AU - Michalak, J. C.

AU - Kuross, S. A.

PY - 2002/8/1

Y1 - 2002/8/1

N2 - Background: Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease. Patients and methods: Thirty-three patients were randomized to either docetaxel (100 mg/m2) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m2) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately. Results: Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35% [95% confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15% to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment. Conclusions: Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.

AB - Background: Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease. Patients and methods: Thirty-three patients were randomized to either docetaxel (100 mg/m2) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m2) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately. Results: Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35% [95% confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15% to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment. Conclusions: Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.

KW - Breast cancer

KW - Chemotherapy

KW - Docetaxel

UR - http://www.scopus.com/inward/record.url?scp=0036668664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036668664&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdf222

DO - 10.1093/annonc/mdf222

M3 - Article

VL - 13

SP - 1225

EP - 1235

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 8

ER -