1. [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].
- Author
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Selle F, Gligorov J, Soares DG, and Lotz JP
- Subjects
- Antineoplastic Agents, Alkylating adverse effects, Bone Neoplasms drug therapy, Female, Humans, Lung Neoplasms drug therapy, Male, Neoplasms drug therapy, Salvage Therapy, Sarcoma drug therapy, Sarcoma, Ewing drug therapy, Small Cell Lung Carcinoma drug therapy, Antineoplastic Agents, Alkylating administration & dosage, Breast Neoplasms drug therapy, Drug Resistance, Neoplasm, Neoplasms, Germ Cell and Embryonal drug therapy, Ovarian Neoplasms drug therapy
- 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., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2016
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