Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer

Nicolaus Kröger, Markus Frick, Oleg Gluz, Svjetlana Mohrmann, Bernd Metzner, Christian Jackisch, Yon Ko, Hans Walter Lindemann, Carl Richard Meier, Hans Peter Lohrmann, Ute Ruffert, Matthias Hänel, Heinrich Bodenstein, Andreas Neubauer, Gerhard Ehninger, Hans Heinrich Wolf, Kathrin Kolbe, Karin Burock, Axel R. Zander, Ulrike Nitz

Research output: Contribution to journalArticle

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Abstract

Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion: Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.

Original languageEnglish (US)
Pages (from-to)3919-3926
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number24
DOIs
StatePublished - Aug 20 2006
Externally publishedYes

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Stem Cell Transplantation
Breast Neoplasms
Drug Therapy
Disease-Free Survival
Thiotepa
Remission Induction
Induction Chemotherapy
Survival
Carboplatin
Cyclophosphamide
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer. / Kröger, Nicolaus; Frick, Markus; Gluz, Oleg; Mohrmann, Svjetlana; Metzner, Bernd; Jackisch, Christian; Ko, Yon; Lindemann, Hans Walter; Meier, Carl Richard; Lohrmann, Hans Peter; Ruffert, Ute; Hänel, Matthias; Bodenstein, Heinrich; Neubauer, Andreas; Ehninger, Gerhard; Wolf, Hans Heinrich; Kolbe, Kathrin; Burock, Karin; Zander, Axel R.; Nitz, Ulrike.

In: Journal of Clinical Oncology, Vol. 24, No. 24, 20.08.2006, p. 3919-3926.

Research output: Contribution to journalArticle

Kröger, N, Frick, M, Gluz, O, Mohrmann, S, Metzner, B, Jackisch, C, Ko, Y, Lindemann, HW, Meier, CR, Lohrmann, HP, Ruffert, U, Hänel, M, Bodenstein, H, Neubauer, A, Ehninger, G, Wolf, HH, Kolbe, K, Burock, K, Zander, AR & Nitz, U 2006, 'Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer', Journal of Clinical Oncology, vol. 24, no. 24, pp. 3919-3926. https://doi.org/10.1200/JCO.2005.04.0352
Kröger, Nicolaus ; Frick, Markus ; Gluz, Oleg ; Mohrmann, Svjetlana ; Metzner, Bernd ; Jackisch, Christian ; Ko, Yon ; Lindemann, Hans Walter ; Meier, Carl Richard ; Lohrmann, Hans Peter ; Ruffert, Ute ; Hänel, Matthias ; Bodenstein, Heinrich ; Neubauer, Andreas ; Ehninger, Gerhard ; Wolf, Hans Heinrich ; Kolbe, Kathrin ; Burock, Karin ; Zander, Axel R. ; Nitz, Ulrike. / Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 24. pp. 3919-3926.
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abstract = "Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33{\%} in the single-dose HDT arm and 37{\%} in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95{\%} CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95{\%} CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95{\%} CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion: Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.",
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T1 - Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer

AU - Kröger, Nicolaus

AU - Frick, Markus

AU - Gluz, Oleg

AU - Mohrmann, Svjetlana

AU - Metzner, Bernd

AU - Jackisch, Christian

AU - Ko, Yon

AU - Lindemann, Hans Walter

AU - Meier, Carl Richard

AU - Lohrmann, Hans Peter

AU - Ruffert, Ute

AU - Hänel, Matthias

AU - Bodenstein, Heinrich

AU - Neubauer, Andreas

AU - Ehninger, Gerhard

AU - Wolf, Hans Heinrich

AU - Kolbe, Kathrin

AU - Burock, Karin

AU - Zander, Axel R.

AU - Nitz, Ulrike

PY - 2006/8/20

Y1 - 2006/8/20

N2 - Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion: Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.

AB - Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion: Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.

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