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Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Gray, Richard ; Liu, Zulian ; Peto, Richard ; Davies, Lucy ; McGale, Paul ; Pan, Hongchao ; Taylor, Carolyn ; Barlow, William ; Bliss, Judith ; Bruzzi, Paolo ; Cameron, David ; Fountzilas, George ; Loibl, Sibylle ; Martin, Miguel ; Möbus, Volker ; Nekljudova, Valentina ; De Placido, Sabino ; Untch, Michael ; Norton, Larry ; Burrett, Julie ; Evans, Vaughan ; Hills, Robert ; James, Sam ; Mannu, Gurdeep ; Morris, Philip ; Wang, Yaochen ; Wang, Zhe ; Gnant, Michael ; Di Leo, Angelo ; Dolci, Stella ; Larsimont, Denis ; Nogaret, Jean Marie ; Piccart, Martine ; Linn, Sabine ; Peer, Petronella ; Tjan-Heijnen, Vivianne ; Vliek, Sonja ; Slamon, Dennis ; Bramwell, Vivien H ; Chen, Bingshu ; Chia, Stephen ; Gelmon, Karen ; Goss, Paul ; Parulekar, Wendy ; Pater, Joseph ; Rakovitch, Eileen ; Shepherd, Lois ; Berry, Don ; Broadwater, Gloria ; Shan, Yi ; Xu, Binghe ; Zhao, Dong-Bing ; Bartelink, Harry ; Cufer, Tanja ; Poortmans, Philip ; Rutgers, Emiel ; van de Velde, Cornelis ; Carrasco, Eva ; Costa, Serban ; Gerber, Bernd ; Jackisch, Christian ; von Minckwitz, Gunter ; Giuliano, Mario ; De Laurentiis, Michele ; Bamia, Christina ; Mavroudis, Dimitris ; A'Hern, Roger ; Sadoon, Mohammad ; Costantino, Joe ; Dignam, James ; Fisher, Bernard ; Mamounas, Eleftherios P ; Paik, Soon ; Redmond, Carol ; Wickerham, D Lawrence ; Venturini, Marco ; Pastorino, Simona ; Sertoli, Mario Roberto ; Albain, Kathy ; Arriagada, Rodrigo ; Bergsten Nordström, Elizabeth ; Boccardo, Francesco ; Coleman, Robert ; Correa, Candace ; Dowsett, Mitch ; Ewertz, Marianne ; Goldhirsch, Aron ; Hill, Catherine ; Jagsi, Reshma ; Janni, Wolfgang ; Mukai, Hirofumi ; Ohashi, Yasuo ; Pierce, Lori ; Raina, Vinod ; Ravdin, Peter ; Rea, Daniel ; Sparano, Joseph ; Tutt, Andrew ; Viale, Giuseppe ; Zambetti, Milvia

The Lancet (British edition), 2019-04, Vol.393 (10179), p.1440-1452 [Periódico revisado por pares]

England: Elsevier Ltd

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Título:
Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials
Autor: Gray, Richard ; Liu, Zulian ; Peto, Richard ; Davies, Lucy ; McGale, Paul ; Pan, Hongchao ; Taylor, Carolyn ; Barlow, William ; Bliss, Judith ; Bruzzi, Paolo ; Cameron, David ; Fountzilas, George ; Loibl, Sibylle ; Martin, Miguel ; Möbus, Volker ; Nekljudova, Valentina ; De Placido, Sabino ; Untch, Michael ; Norton, Larry ; Burrett, Julie ; Evans, Vaughan ; Hills, Robert ; James, Sam ; Mannu, Gurdeep ; Morris, Philip ; Wang, Yaochen ; Wang, Zhe ; Gnant, Michael ; Di Leo, Angelo ; Dolci, Stella ; Larsimont, Denis ; Nogaret, Jean Marie ; Piccart, Martine ; Linn, Sabine ; Peer, Petronella ; Tjan-Heijnen, Vivianne ; Vliek, Sonja ; Slamon, Dennis ; Bramwell, Vivien H ; Chen, Bingshu ; Chia, Stephen ; Gelmon, Karen ; Goss, Paul ; Parulekar, Wendy ; Pater, Joseph ; Rakovitch, Eileen ; Shepherd, Lois ; Berry, Don ; Broadwater, Gloria ; Shan, Yi ; Xu, Binghe ; Zhao, Dong-Bing ; Bartelink, Harry ; Cufer, Tanja ; Poortmans, Philip ; Rutgers, Emiel ; van de Velde, Cornelis ; Carrasco, Eva ; Costa, Serban ; Gerber, Bernd ; Jackisch, Christian ; von Minckwitz, Gunter ; Giuliano, Mario ; De Laurentiis, Michele ; Bamia, Christina ; Mavroudis, Dimitris ; A'Hern, Roger ; Sadoon, Mohammad ; Costantino, Joe ; Dignam, James ; Fisher, Bernard ; Mamounas, Eleftherios P ; Paik, Soon ; Redmond, Carol ; Wickerham, D Lawrence ; Venturini, Marco ; Pastorino, Simona ; Sertoli, Mario Roberto ; Albain, Kathy ; Arriagada, Rodrigo ; Bergsten Nordström, Elizabeth ; Boccardo, Francesco ; Coleman, Robert ; Correa, Candace ; Dowsett, Mitch ; Ewertz, Marianne ; Goldhirsch, Aron ; Hill, Catherine ; Jagsi, Reshma ; Janni, Wolfgang ; Mukai, Hirofumi ; Ohashi, Yasuo ; Pierce, Lori ; Raina, Vinod ; Ravdin, Peter ; Rea, Daniel ; Sparano, Joseph ; Tutt, Andrew ; Viale, Giuseppe ; Zambetti, Milvia
Assuntos: Anthracycline ; Antineoplastic Agents - administration & dosage ; Bibliographic data bases ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer ; Cancer therapies ; Chemotherapy ; Clinical trials ; Collaboration ; Colony-stimulating factor ; Cytotoxicity ; Dosage ; Drug Administration Schedule ; Drug dosages ; Drugs ; Evidence-based medicine ; Female ; Health risk assessment ; Health risks ; Histology ; Humans ; Information sharing ; Intervals ; Medical research ; Medicin och hälsovetenskap ; Meta-analysis ; Mortality ; Oncology ; Patients ; Randomization ; Risk assessment ; Schedules ; Systematic review ; Taxanes ; Tumors ; Womens health
É parte de: The Lancet (British edition), 2019-04, Vol.393 (10179), p.1440-1452
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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Full list of members available at https://www.ctsu.ox.ac.uk/research/ebctcg
Descrição: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes. Cancer Research UK, Medical Research Council.
Editor: England: Elsevier Ltd
Idioma: Inglês

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Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

England: Elsevier Ltd

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