title: [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].
abstract: The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.
authors.affiliation: Assistance publique-Hôpitaux de Paris (AP-HP), hôpital Tenon, service d'oncologie médicale et de thérapie cellulaire, alliance pour la recherche en cancérologie (APREC), 4, rue de la Chine, 75970 Paris cedex 20, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Selle
authors.affiliation: Assistance publique-Hôpitaux de Paris (AP-HP), hôpital Tenon, service d'oncologie médicale et de thérapie cellulaire, alliance pour la recherche en cancérologie (APREC), 4, rue de la Chine, 75970 Paris cedex 20, France; Université Pierre-et-Marie-Curie (UPMC Univ Paris 06), Sorbonne universités, institut universitaire de cancérologie, 4, place Jussieu, 75005 Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.affiliation: Assistance publique-Hôpitaux de Paris (AP-HP), hôpital Tenon, service d'oncologie médicale et de thérapie cellulaire, alliance pour la recherche en cancérologie (APREC), 4, rue de la Chine, 75970 Paris cedex 20, France.
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Soares
authors.affiliation: Assistance publique-Hôpitaux de Paris (AP-HP), hôpital Tenon, service d'oncologie médicale et de thérapie cellulaire, alliance pour la recherche en cancérologie (APREC), 4, rue de la Chine, 75970 Paris cedex 20, France; Université Pierre-et-Marie-Curie (UPMC Univ Paris 06), Sorbonne universités, institut universitaire de cancérologie, 4, place Jussieu, 75005 Paris, France. Electronic address: jean-pierre.lotz@aphp.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lotz
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016879:Salvage Therapy; D012509:Sarcoma / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy
chemical_list: D018906:Antineoplastic Agents, Alkylating
keywords: Autogreffe de cellules-souches; Autologous stem cell transplant; Breast cancer; Cancer de l’ovaire; Cancer du sein; Germ cell tumors; Hautes doses de chimiothérapie; High-dose chemotherapy; Ovarian cancer; Solid tumors; Tumeurs germinales; Tumeurs solides