High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Support for Solid Tumors in Adults Paolo Pedrazzoli a , Giovanni Rosti b , Simona Secondino a , Ornella Carminati c , and Taner Demirer d on behalf of the European Group for Blood and Marrow Transplantation, Solid Tumors Working Party and Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare Supported by experimental evidence and convincing results of early phase II studies, since the 1980s high-dose chemotherapy (HDC) with autologous hematopoietic stem cell sup- port (AHSCT) has been uncritically adopted by many oncologists as a potentially curative option for several solid tumors. As a result, the number (and size) of randomized trials comparing this approach with conventional chemotherapy initiated (and often abandoned before completion) in this setting was limited and the benefit of a greater escalation of dose of chemotherapy with stem cell transplantation in solid tumors remains, with the possible exception of breast carcinoma (BC) and germ cell tumors (GCT), largely unsettled. In this article, we review and comment on the data from studies to date of HDC for solid tumors in adults. Semin Hematol 44:286-295 © 2007 Elsevier Inc. All rights reserved. H igh-dose chemotherapy (HDC) with autologous hema- topoietic stem cell transplantation (AHSCT) was first introduced as an experimental treatment for solid tumors in the late 1970s. 1 The premise for such treatment was ex- tremely simple: if you give more, you may achieve more (or if you prefer: can grams work when milligrams fail?). Initial data concerned pediatric tumors, but were rapidly followed by an incredible amount of data on germ cell tumors (GCT), breast carcinoma (BC), sarcomas, small cell lung cancer (SCLC), ovarian cancers, and nearly all other tumor types, although many of the reports were anecdotal. After more than a quarter of a century of investigations, we are now in a position to analyze what happened and why some questions received an answer and others did not. The “rush to transplantation” in the early days led to thousands of patients being treated with this modality, BC being the most frequent indication with nearly 2,000 patients per year in the late 1990s in Europe alone. 2 Unfortunately, the vast majority of patients were treated outside of clinical trials. So for many years the level of evidence remained low. Nevertheless, some important randomized studies were conducted, and some robust data emerged at least for some tumor types. The history of HDC with AHSCT for solid tumors has seen waves of optimism followed by waves of pessimism, some- times seeming to be at the beginning of the end, other times at the end of the beginning. The question remains whether “more is better?” This review will try to clarify what happened and where we are now in this still fascinating and not yet exhausted field. We will first take into consideration BC due to numerous data available on this tumor type, and subse- quently the other tumors for which HDC has been widely used. Breast Carcinoma Several nonrandomized studies conducted in the 1980s and early 1990s demonstrated unusual improvements in patients with BC receiving HDC. 3–5 This led to the premature accep- a Divisione di Oncologia Medica Falck, Ospedale Niguarda Ca’ Granda, Mi- lano, Italy. b Oncologia Medica, Ospedale Regionale, Treviso, Italy. c Department of Oncology, Forli, Italy. d Department of Hematology, Ankara University Medical School, Ibni Sina Hospital, Ankara, Turkey. Supported in part by grant regionale 2005, Associazione Italiana per la Ricerca sul Cancro (AIRC) to P.P. and Oncologia Ca’ Granda ONLUS Fondazione to P.P. and S.S Address correspondence to Taner Demirer, MD, FACP, Department of He- matology/Oncology, Ankara University Medical School, Cebeci Hospi- tal, Ankara, Turkey. E-mail: Taner.Demirer@medicine.ankara.edu.tr 286 0037-1963/07/$-see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.seminhematol.2007.08.009