Neoadjuvant chemotherapy with sequential anthracycline-docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem)

N McCarthy; F Boyle; N Zdenkowski; J Bull; E Leong; A Simpson; G Kannourakis; P A Francis; J Chirgwin; E Abdi; V Gebski; A S Veillard; D Zannino; N Wilcken; L Reaby; D F Lindsay; H D Badger; J F Forbes; Australia and New Zealand Breast Cancer Trials Group

doi:10.1016/j.breast.2013.12.001

Neoadjuvant chemotherapy with sequential anthracycline-docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem)

Breast. 2014 Apr;23(2):142-51. doi: 10.1016/j.breast.2013.12.001. Epub 2014 Jan 3.

Authors

N McCarthy¹, F Boyle², N Zdenkowski³, J Bull⁴, E Leong⁴, A Simpson⁵, G Kannourakis⁶, P A Francis⁷, J Chirgwin⁸, E Abdi⁹, V Gebski¹⁰, A S Veillard¹⁰, D Zannino¹⁰, N Wilcken¹¹, L Reaby⁴, D F Lindsay⁴, H D Badger⁴, J F Forbes¹²; Australia and New Zealand Breast Cancer Trials Group

Affiliations

¹ Cancer Care Services, Royal Brisbane and Women's Hospital, Butterfield St, Herston, Brisbane, QLD 4029, Australia; University of Queensland, Brisbane, QLD, Australia. Electronic address: NMcCarthy@iconcancercare.com.au.
² The Mater Hospital, Sydney, NSW, Australia; University of Sydney, Sydney, NSW, Australia.
³ Australia and New Zealand Breast Cancer Trials Group, Newcastle, NSW, Australia; University of Newcastle, Newcastle, NSW, Australia.
⁴ Australia and New Zealand Breast Cancer Trials Group, Newcastle, NSW, Australia.
⁵ Wellington Cancer Centre, Wellington Hospital, Wellington, New Zealand.
⁶ Ballarat Oncology and Haematology Service, Ballarat, VIC, Australia.
⁷ Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Medicine, St. Vincent's Hospital, University of Melbourne, VIC, Australia.
⁸ University of Newcastle, Newcastle, NSW, Australia; Box Hill Hospital, Box Hill, VIC, Australia; Maroondah Breast Clinic, Maroondah Hospital, Ringwood East, VIC, Australia; Monash University, VIC, Australia.
⁹ Tweed Hospital, Tweed Heads, NSW, Australia; Griffith University- Gold Coast, Southport, QLD, Australia.
¹⁰ National Health and Medical Research Council Clinical Trials Centre, Sydney, NSW, Australia.
¹¹ Westmead Cancer Care Centre, Westmead Hospital, University of Sydney, NSW, Australia.
¹² Australia and New Zealand Breast Cancer Trials Group, Newcastle, NSW, Australia; University of Newcastle, Newcastle, NSW, Australia; Department of Surgical Oncology, Calvary Mater Newcastle, Newcastle, NSW, Australia.

PMID: 24393617
DOI: 10.1016/j.breast.2013.12.001

Abstract

Background: Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy.

Methods: Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety.

Results: 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer.

Conclusion: Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.

Keywords: Gemcitabine; Locally advanced breast cancer; Neoadjuvant chemotherapy; Pathologic complete response; Phase 2.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Anthracyclines / therapeutic use*
Antibodies, Monoclonal, Humanized / adverse effects
Antibodies, Monoclonal, Humanized / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Breast Neoplasms / drug therapy*
Breast Neoplasms / pathology
Cyclophosphamide / adverse effects
Cyclophosphamide / therapeutic use*
Deoxycytidine / adverse effects
Deoxycytidine / analogs & derivatives*
Deoxycytidine / therapeutic use
Disease-Free Survival
Docetaxel
Epirubicin / adverse effects
Epirubicin / therapeutic use*
Female
Gemcitabine
Humans
Middle Aged
Neoadjuvant Therapy*
Taxoids / adverse effects
Taxoids / therapeutic use*
Trastuzumab
Treatment Outcome

Substances

Anthracyclines
Antibodies, Monoclonal, Humanized
Taxoids
Deoxycytidine
Docetaxel
Epirubicin
Cyclophosphamide
Trastuzumab
Gemcitabine

Associated data

ANZCTR/ACTRN12606000191594