Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy
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Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.
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chemotherapy dendritic cells immunotherapy metronomic Treg vaccine 5 aza 2' deoxycytidine adenovirus vector antineoplastic agent bevacizumab celecoxib cetuximab cisplatin cyclophosphamide dendritic cell vaccine docetaxel doxorubicin etoposide fluorouracil folinic acid gemcitabine granulocyte colony stimulating factor idarubicin interleukin 12 irinotecan mercaptopurine methotrexate mitomycin mitoxantrone oxaliplatin paclitaxel rofecoxib tumor cell vaccine unindexed drug vinblastine vincristine advanced cancer alopecia antiangiogenic activity antineoplastic activity arthralgia bleeding blood toxicity bone marrow suppression brain damage breast cancer breast metastasis cancer chemotherapy cancer combination chemotherapy cancer immunotherapy cancer resistance colon cancer colon carcinoma colorectal cancer cytokine response cytotoxic T lymphocyte depression digestive system function disorder DNA methylation dose calculation dose response drug cytotoxicity drug megadose drug potentiation drug safety drug sensitivity heat injury Hodgkin disease human immunological tolerance immunomodulation immunostimulation infection leukemia leukopenia liver toxicity low dose metronomic chemotherapy low drug dose lung carcinoma lung non small cell cancer lymphocytopenia lymphoma maintenance therapy malignant neoplastic disease maximum tolerated dose melanoma mucosal disease multiple myeloma neoplasm neuroblastoma neutropenia nonhuman ovary cancer priority journal review side effect single drug dose stomach tumor T cell depletion thrombocytopenia thromboembolism viral gene delivery system weight reduction Animals Antineoplastic Agents Combined Modality Therapy Humans Immunologic Factors Immunotherapy Neoplasms
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International Journal of Cancer, v. 132, n. 11, p. 2471-2478, 2013.
