1. 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
- Author
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Richard Gray, Rosie Bradley, Jeremy Braybrooke, Zulian Liu, Richard Peto, Lucy Davies, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, William Barlow, Judith Bliss, Paolo Bruzzi, David Cameron, George Fountzilas, Sibylle Loibl, John Mackey, Miguel Martin, Lucia Del Mastro, Volker Möbus, Valentina Nekljudova, Sabino De Placido, Sandra Swain, Michael Untch, Kathleen I Pritchard, Jonas Bergh, Larry Norton, Clare Boddington, Julie Burrett, Mike Clarke, Christina Davies, Fran Duane, Vaughan Evans, Lucy Gettins, Jon Godwin, Robert Hills, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Yaochen Wang, Zhe Wang, Peter Fasching, Nadia Harbeck, Pascal Piedbois, Michael Gnant, Guenther Steger, Angelo Di Leo, Stella Dolci, Prue Francis, Denis Larsimont, Jean Marie Nogaret, Catherine Philippson, Martine Piccart, Sabine Linn, Petronella Peer, Vivianne Tjan-Heijnen, Sonja Vliek, Dennis Slamon, John Bartlett, Vivien H Bramwell, Bingshu Chen, Stephen Chia, Karen Gelmon, Paul Goss, Mark Levine, Wendy Parulekar, Joseph Pater, Eileen Rakovitch, Lois Shepherd, Dongsheng Tu, Tim Whelan, Don Berry, Gloria Broadwater, Constance Cirrincione, Hyman Muss, Raymond Weiss, Yi Shan, Yong Fu Shao, Xiang Wang, Binghe Xu, Dong-Bing Zhao, Harry Bartelink, Nina Bijker, Jan Bogaerts, Fatima Cardoso, Tanja Cufer, Jean-Pierre Julien, Philip Poortmans, Emiel Rutgers, Cornelis van de Velde, Eva Carrasco, Miguel Angel Segui, Jens Uwe Blohmer, Serban Costa, Bernd Gerber, Christian Jackisch, Gunter von Minckwitz, Mario Giuliano, Michele De Laurentiis, Christina Bamia, Georgia-Angeliki Koliou, Dimitris Mavroudis, Roger A'Hern, Paul Ellis, Lucy Kilburn, James Morden, John Yarnold, Mohammad Sadoon, Augustinus H Tulusan, Stewart Anderson, Gordon Bass, Joe Costantino, James Dignam, Bernard Fisher, Charles Geyer, Eleftherios P Mamounas, Soon Paik, Carol Redmond, D Lawrence Wickerham, Marco Venturini, Claudia Bighin, Simona Pastorino, Paolo Pronzato, Mario Roberto Sertoli, Theodorus Foukakis, Kathy Albain, Rodrigo Arriagada, Elizabeth Bergsten Nordström, Francesco Boccardo, Etienne Brain, Lisa Carey, Alan Coates, Robert Coleman, Candace Correa, Jack Cuzick, Nancy Davidson, Mitch Dowsett, Marianne Ewertz, John Forbes, Richard Gelber, Aron Goldhirsch, Pamela Goodwin, Daniel Hayes, Catherine Hill, James Ingle, Reshma Jagsi, Wolfgang Janni, Hirofumi Mukai, Yasuo Ohashi, Lori Pierce, Vinod Raina, Peter Ravdin, Daniel Rea, Meredith Regan, John Robertson, Joseph Sparano, Andrew Tutt, Giuseppe Viale, Nicholas Wilcken, Norman Wolmark, Wiliam Wood, Milvia Zambetti, Gray, R., Bradley, R., Braybrooke, J., Liu, Z., Peto, R., Davies, L., Dodwell, D., Mcgale, P., Pan, H., Taylor, C., Barlow, W., Bliss, J., Bruzzi, P., Cameron, D., Fountzilas, G., Loibl, S., Mackey, J., Martin, M., Del Mastro, L., Mobus, V., Nekljudova, V., De Placido, S., Swain, S., Untch, M., Pritchard, K. I., Bergh, J., Norton, L., Boddington, C., Burrett, J., Clarke, M., Davies, C., Duane, F., Evans, V., Gettins, L., Godwin, J., Hills, R., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Wang, Y., Wang, Z., Fasching, P., Harbeck, N., Piedbois, P., Gnant, M., Steger, G., Di Leo, A., Dolci, S., Francis, P., Larsimont, D., Nogaret, J. M., Philippson, C., Piccart, M., Linn, S., Peer, P., Tjan-Heijnen, V., Vliek, S., Slamon, D., Bartlett, J., Bramwell, V. H., Chen, B., Chia, S., Gelmon, K., Goss, P., Levine, M., Parulekar, W., Pater, J., Rakovitch, E., Shepherd, L., Tu, D., Whelan, T., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Weiss, R., Shan, Y., Shao, Y. F., Wang, X., Xu, B., Zhao, D. -B., Bartelink, H., Bijker, N., Bogaerts, J., Cardoso, F., Cufer, T., Julien, J. -P., Poortmans, P., Rutgers, E., van de Velde, C., Carrasco, E., Segui, M. A., Blohmer, J. U., Costa, S., Gerber, B., Jackisch, C., von Minckwitz, G., Giuliano, M., De Laurentiis, M., Bamia, C., Koliou, G. -A., Mavroudis, D., A'Hern, R., Ellis, P., Kilburn, L., Morden, J., Yarnold, J., Sadoon, M., Tulusan, A. H., Anderson, S., Bass, G., Costantino, J., Dignam, J., Fisher, B., Geyer, C., Mamounas, E. P., Paik, S., Redmond, C., Wickerham, D. L., Venturini, M., Bighin, C., Pastorino, S., Pronzato, P., Sertoli, M. R., Foukakis, T., Albain, K., Arriagada, R., Bergsten Nordstrom, E., Boccardo, F., Brain, E., Carey, L., Coates, A., Coleman, R., Correa, C., Cuzick, J., Davidson, N., Dowsett, M., Ewertz, M., Forbes, J., Gelber, R., Goldhirsch, A., Goodwin, P., Hayes, D., Hill, C., Ingle, J., Jagsi, R., Janni, W., Mukai, H., Ohashi, Y., Pierce, L., Raina, V., Ravdin, P., Rea, D., Regan, M., Robertson, J., Sparano, J., Tutt, A., Viale, G., Wilcken, N., Wolmark, N., Wood, W., and Zambetti, M.
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Oncology ,treatment schedule ,medicine.medical_specialty ,Anthracycline ,medicine.medical_treatment ,novotvorbe dojk ,Antineoplastic Agents ,Breast Neoplasms ,režim zdravljenja ,Disease ,randomized trials ,030204 cardiovascular system & hematology ,chemotherapy ,meta-analiza ,klinični protokoli ,Drug Administration Schedule ,randomizirane raziskave ,Antineoplastic Agent ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Internal medicine ,breast neoplasms ,medicine ,Humans ,clinical protocols ,terapija z zdravili ,030212 general & internal medicine ,Early breast cancer ,Chemotherapy ,Taxane ,business.industry ,rak dojk ,kemoterapija ,General Medicine ,medicine.disease ,Dose intensity ,udc:618.19-006 ,drug therapy ,meta-analysis ,Meta-analysis ,Female ,women ,ženske ,business ,Breast Neoplasm - Abstract
Background 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. Methods 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). Findings 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 Interpretation 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.
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- 2019