Gunter von Minckwitz1,2, Bettina Conrad3, Toralf Reimer4, Thomas Decker5, Holger Eidtmann6, Wolfgang Eiermann7, John Hackmann8, Volker Möbus9, Frederik Marmé10, Jochem Potenberg11, Elmar Stickeler12, Eike Simon13, Christoph Thomssen14, Jens Huober15, Carsten Denkert16, Joachim Alfer17, Christian Jackisch18, Valentina Nekljudova1, Nicole Burchardi1, Sibylle Loibl1,18. 1. German Breast Group, Neu-Isenburg, Germany. 2. Department of Gynecology and Obstetrics, University Hospital Frankfurt, Frankfurt, Germany. 3. Elisabeth Hospital, Kassel, Germany. 4. Department Obstetrics and Gynecology, Sudstadt Clinic, Rostock, Germany. 5. Study Centre Oncology, Ravensburg, Germany. 6. Department of Gynecology and Obstetrics, University Hospital Kiel, Kiel, Germany. 7. Interdisciplinary Centre Munich, Munich, Germany. 8. Department of Obstetrics and Gynecology, Marienhospital, Witten, Germany. 9. Department of Obstetrics and Gynecology, Hoechst Clinic, Frankfurt, Germany. 10. University Women's Hospital, Heidelberg, Germany. 11. Department of Obstetrics and Gynecology, Ev. Waldkrankenhaus Hospital, Berlin, Germany. 12. University Women's Hospital, Freiburg, Germany. 13. Department of Obstetrics and Gynecology, Kreiskrankenhaus Torgau, Torgau, Germany. 14. University Women's Hospital, Halle, Germany. 15. University Women's Hospital, Ulm, Germany. 16. Berlin Charity Hospital, Institute of Pathology, Berlin, Germany. 17. Institute of Pathology Kaufbeuren-Ravensburg, Germany. 18. Department of Gynecology Obstetrics and Gynecology, Sana Clinic, Offenbach, Germany.
Abstract
BACKGROUND: Although greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane-based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients. METHODS:Patients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI-1 or any stagepT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m(2) and cyclophosphamide at a dose of 600 mg/m(2) intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m(2), methotrexate at a dose of 40 mg/m(2), and 5-fluorouracil at a dose of 600 mg/m(2) iv on days 1 plus 8 every 29 days) versus 6 cycles of nab-paclitaxel and capecitabine (nPX) (nab-paclitaxel at a dose of 100 mg/m(2) iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m(2) orally on days 1-14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events. RESULTS: Thirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P<.001) with 1 and 5 deaths observed during treatment, respectively. Grade 3 to 5 adverse events were more frequent among patients treated with EC/CMF (90.9%) than among those treated with nPX (64.8%) (P<.001), with hematological toxicities being more frequent with EC/CMF (88.4% vs 22.3%; P<.001), but nonhematological toxicities (hand-foot syndrome, diarrhea, mucositis, fatigue, sensory neuropathy, thromboembolisms, and metabolic disorders) being more frequent with nPX (58.5% vs 18.7%; P<.001). None of the geriatric scores (Charlson comorbidity index, Vulnerable Elders Survey [VES-13], Instrumental Activities of Daily Living [IADL], and G8) independently predicted grade 3 to 5 toxic events or treatment discontinuations. No differences in survival between the treatment groups were observed after 22.8 months. CONCLUSIONS: Compared with EC/CMF, treatment with nPX led to more treatment discontinuations and nonhematological toxicities in elderly patients with moderate or high-risk breast cancer.
RCT Entities:
BACKGROUND: Although greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane-based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients. METHODS:Patients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either humanepidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI-1 or any stage pT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m(2) and cyclophosphamide at a dose of 600 mg/m(2) intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m(2), methotrexate at a dose of 40 mg/m(2), and 5-fluorouracil at a dose of 600 mg/m(2) iv on days 1 plus 8 every 29 days) versus 6 cycles of nab-paclitaxel and capecitabine (nPX) (nab-paclitaxel at a dose of 100 mg/m(2) iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m(2) orally on days 1-14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events. RESULTS: Thirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P<.001) with 1 and 5 deaths observed during treatment, respectively. Grade 3 to 5 adverse events were more frequent among patients treated with EC/CMF (90.9%) than among those treated with nPX (64.8%) (P<.001), with hematological toxicities being more frequent with EC/CMF (88.4% vs 22.3%; P<.001), but nonhematological toxicities (hand-foot syndrome, diarrhea, mucositis, fatigue, sensory neuropathy, thromboembolisms, and metabolic disorders) being more frequent with nPX (58.5% vs 18.7%; P<.001). None of the geriatric scores (Charlson comorbidity index, Vulnerable Elders Survey [VES-13], Instrumental Activities of Daily Living [IADL], and G8) independently predicted grade 3 to 5 toxic events or treatment discontinuations. No differences in survival between the treatment groups were observed after 22.8 months. CONCLUSIONS: Compared with EC/CMF, treatment with nPX led to more treatment discontinuations and nonhematological toxicities in elderly patients with moderate or high-risk breast cancer.
Authors: Hyman B Muss; Mei-Yin C Polley; Donald A Berry; Heshan Liu; Constance T Cirrincione; Maria Theodoulou; Ann M Mauer; Alice B Kornblith; Ann H Partridge; Lynn G Dressler; Harvey J Cohen; Patricia A Kartcheske; Edith A Perez; Antonio C Wolff; Julie R Gralow; Harold J Burstein; Ahmad A Mahmood; Linda M Sutton; Gustav Magrinat; Barbara A Parker; Ronald D Hart; Debjani Grenier; Arti Hurria; Aminah Jatoi; Larry Norton; Clifford A Hudis; Eric P Winer; Lisa Carey Journal: J Clin Oncol Date: 2019-07-24 Impact factor: 44.544
Authors: Melina L Willson; Lucinda Burke; Thomas Ferguson; Davina Ghersi; Anna K Nowak; Nicholas Wilcken Journal: Cochrane Database Syst Rev Date: 2019-09-02
Authors: Siao-Nge Hoon; Peter Kh Lau; Alison M White; Max K Bulsara; Patricia D Banks; Andrew D Redfern Journal: Cochrane Database Syst Rev Date: 2021-05-26