PURPOSE: High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. METHODS: We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. RESULTS: The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. CONCLUSION: Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy.
PURPOSE: High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. METHODS: We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. RESULTS: The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. CONCLUSION: Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy.
Authors: Jean-Pierre Lotz; Hervé Curé; Maud Janvier; Bernard Asselain; François Morvan; Michel Legros; Bruno Audhuy; Pierre Biron; Maryse Guillemot; Jocelyne Goubet; Abderrahmane Laadem; Christian Cailliot; Christine Le Maignan; Thierry Delozier; Sylvie Glaisner; Dominique Maraninchi; Henri Roché; Christian Gisselbrecht Journal: Eur J Cancer Date: 2005-01 Impact factor: 9.162
Authors: Donald A Berry; Gloria Broadwater; John P Klein; Karen Antman; Joseph Aisner; Jacob Bitran; Mary Costanza; Cesar O Freytes; Edward Stadtmauer; Robert Peter Gale; I Craig Henderson; Hillard M Lazarus; Philip L McCarthy; Larry Norton; Howard Parnes; Andrew Pecora; Michael C Perry; Philip Rowlings; Gary Spitzer; Mary M Horowitz Journal: J Clin Oncol Date: 2002-02-01 Impact factor: 44.544
Authors: Donald A Berry; Naoto T Ueno; Marcella M Johnson; Xiudong Lei; Jean Caputo; Sjoerd Rodenhuis; William P Peters; Robert C Leonard; William E Barlow; Martin S Tallman; Jonas Bergh; Ulrike A Nitz; Alessandro M Gianni; Russell L Basser; Axel R Zander; R Charles Coombes; Henri Roché; Yutaka Tokuda; Elisabeth G E de Vries; Gabriel N Hortobagyi; John P Crown; Paolo Pedrazzoli; Marco Bregni; Taner Demirer Journal: J Clin Oncol Date: 2011-07-18 Impact factor: 44.544
Authors: K H Antman; P A Rowlings; W P Vaughan; C J Pelz; J W Fay; K K Fields; C O Freytes; R P Gale; B E Hillner; H K Holland; M J Kennedy; J P Klein; H M Lazarus; P L McCarthy; R Saez; G Spitzer; E A Stadtmauer; S F Williams; S Wolff; K A Sobocinski; J O Armitage; M M Horowitz Journal: J Clin Oncol Date: 1997-05 Impact factor: 44.544
Authors: E A Stadtmauer; A O'Neill; L J Goldstein; P A Crilley; K F Mangan; J N Ingle; I Brodsky; S Martino; H M Lazarus; J K Erban; C Sickles; J H Glick Journal: N Engl J Med Date: 2000-04-13 Impact factor: 91.245
Authors: A VanderWalde; W Ye; P Frankel; D Asuncion; L Leong; T Luu; R Morgan; P Twardowski; M Koczywas; R Pezner; I B Paz; K Margolin; J Wong; J H Doroshow; S Forman; S Shibata; G Somlo Journal: Biol Blood Marrow Transplant Date: 2012-02-02 Impact factor: 5.742
Authors: David A Palma; Joseph K Salama; Simon S Lo; Suresh Senan; Tom Treasure; Ramaswamy Govindan; Ralph Weichselbaum Journal: Nat Rev Clin Oncol Date: 2014-06-24 Impact factor: 66.675
Authors: Donald A Berry; Naoto T Ueno; Marcella M Johnson; Xiudong Lei; Jean Caputo; Sjoerd Rodenhuis; William P Peters; Robert C Leonard; William E Barlow; Martin S Tallman; Jonas Bergh; Ulrike A Nitz; Alessandro M Gianni; Russell L Basser; Axel R Zander; R Charles Coombes; Henri Roché; Yutaka Tokuda; Elisabeth G E de Vries; Gabriel N Hortobagyi; John P Crown; Paolo Pedrazzoli; Marco Bregni; Taner Demirer Journal: J Clin Oncol Date: 2011-07-18 Impact factor: 44.544