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Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer : a randomised trial

Bergh, J ; Wiklund, T ; Erikstein, B ; Lidbrink, E ; Lindman, H ; Malmström, Per LU ; Kellokumpu-Lehtinen, P ; Bengtsson, N O ; Söderlund, G and Anker, G , et al. (2000) In The Lancet 356(9239). p.1384-1391
Abstract

BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support.

METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard... (More)

BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support.

METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat.

FINDINGS: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome.

INTERPRETATION: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.

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publishing date
type
Contribution to journal
publication status
published
keywords
Acute Disease, Adult, Algorithms, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Breast Neoplasms/drug therapy, Carboplatin/administration & dosage, Chemotherapy, Adjuvant, Combined Modality Therapy, Cyclophosphamide/administration & dosage, Disease-Free Survival, Epirubicin/administration & dosage, Female, Fluorouracil/administration & dosage, Granulocyte Colony-Stimulating Factor/therapeutic use, Hematopoietic Stem Cell Transplantation, Humans, Infusions, Intravenous, Leukemia, Myeloid/chemically induced, Lymphatic Metastasis, Mastectomy, Segmental, Middle Aged, Proportional Hazards Models, Sweden, Thiotepa/administration & dosage
in
The Lancet
volume
356
issue
9239
pages
1384 - 1391
publisher
Elsevier
external identifiers
  • pmid:11052580
  • scopus:0034699950
ISSN
0140-6736
DOI
10.1016/s0140-6736(00)02841-5
language
English
LU publication?
no
id
496d5104-39e9-4bef-b4f1-361c0aa84c11
date added to LUP
2022-03-02 11:06:36
date last changed
2025-01-11 09:05:36
@article{496d5104-39e9-4bef-b4f1-361c0aa84c11,
  abstract     = {{<p>BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support.</p><p>METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat.</p><p>FINDINGS: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p&lt;0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome.</p><p>INTERPRETATION: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.</p>}},
  author       = {{Bergh, J and Wiklund, T and Erikstein, B and Lidbrink, E and Lindman, H and Malmström, Per and Kellokumpu-Lehtinen, P and Bengtsson, N O and Söderlund, G and Anker, G and Wist, E and Ottosson, S and Salminen, E and Ljungman, P and Holte, H and Nilsson, J and Blomqvist, C and Wilking, Nils}},
  issn         = {{0140-6736}},
  keywords     = {{Acute Disease; Adult; Algorithms; Antineoplastic Combined Chemotherapy Protocols/administration & dosage; Breast Neoplasms/drug therapy; Carboplatin/administration & dosage; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide/administration & dosage; Disease-Free Survival; Epirubicin/administration & dosage; Female; Fluorouracil/administration & dosage; Granulocyte Colony-Stimulating Factor/therapeutic use; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Leukemia, Myeloid/chemically induced; Lymphatic Metastasis; Mastectomy, Segmental; Middle Aged; Proportional Hazards Models; Sweden; Thiotepa/administration & dosage}},
  language     = {{eng}},
  number       = {{9239}},
  pages        = {{1384--1391}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet}},
  title        = {{Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer : a randomised trial}},
  url          = {{http://dx.doi.org/10.1016/s0140-6736(00)02841-5}},
  doi          = {{10.1016/s0140-6736(00)02841-5}},
  volume       = {{356}},
  year         = {{2000}},
}