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. 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.
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.
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.
Authors: Li Yan Lim; Hui Miao; Joline S J Lim; Soo Chin Lee; Nirmala Bhoo-Pathy; Cheng Har Yip; Nur Aishah B M Taib; Patrick Chan; Ern Yu Tan; Swee Ho Lim; Geok Hoon Lim; Evan Woo; Yia Swam Tan; Jung Ah Lee; Mabel Wong; Puay Hoon Tan; Kong Wee Ong; Fuh Yong Wong; Yoon Sim Yap; Mikael Hartman Journal: Cancer Med Date: 2016-12-20 Impact factor: 4.452
Authors: Ye Won Jeon; Tae Hyun Kim; Hyun Jo Youn; Sehwan Han; Yongsik Jung; Geumhee Gwak; Young Sam Park; Jeong Soo Kim; Young Jin Suh Journal: J Breast Cancer Date: 2017-12-19 Impact factor: 3.588