Abstract
Metronomic chemotherapy (MC) refers to the close administration of a chemotherapeutic drug for a long time with no extended drug-free breaks. It was developed to overcome drug resistance, partly by shifting the therapeutic target from tumor cells to the tumor vasculature, with less toxicity. Because of this peculiar way of administration, MC can be viewed as a form of long-term 'maintenance' treatment, and can be integrated with standard and conventional chemotherapy in a "chemo-switching" strategy. Additional mechanisms are involved in its antitumor activity, such as activation of immunity, induction of tumor dormancy, chemotherapy-driven dependency of cancer cells, and the '4D effect'. In this paper we report the most important studies that have analyzed these processes. In fact, a number of preclinical and clinical studies in solid tumors as well as in multiple myeloma, have been reported regarding several chemotherapy drugs which have been proposed with a metronomic schedule: vinorelbine, cyclophosphamide, capecitabine, methotrexate, bevacizumab, etoposide, gemcitabine, sorafenib, everolimus and temozolomide. The results of these studies have been sometimes conflicting, highlighting the need to develop reliable tools for patient selection and stratification. However, a more precise evaluation of MC strategies with the ongoing randomized phase II/III clinical is fundamental, because of the strict correlation of this approach with translational research and target therapy. Moreover, because of the low toxicity of MC, these studies will also help to better evaluate the clinical benefit of this treatment, with a special focus on elderly and low performance status patients.
| Original language | English |
|---|---|
| Pages (from-to) | 46-61 |
| Number of pages | 16 |
| Journal | Critical Reviews in Oncology/Hematology |
| Volume | 95 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 1 2015 |
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Keywords
- Angiogenesis
- Bevacizumab
- Chemo-switching
- Cyclophosphamide
- Immunity
- Maintenance
- Metronomic chemotherapy
- Toxicity
ASJC Scopus subject areas
- Oncology
- Hematology
- Geriatrics and Gerontology
Cite this
Metronomic chemotherapy from rationale to clinical studies : A dream or reality? / Gnoni, Antonio; Silvestris, Nicola; Licchetta, Antonella; Santini, Daniele; Scartozzi, Mario; Ria, Roberto; Pisconti, Salvatore; Petrelli, Fausto; Vacca, Angelo; Lorusso, Vito.
In: Critical Reviews in Oncology/Hematology, Vol. 95, No. 1, 01.07.2015, p. 46-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metronomic chemotherapy from rationale to clinical studies
T2 - A dream or reality?
AU - Gnoni, Antonio
AU - Silvestris, Nicola
AU - Licchetta, Antonella
AU - Santini, Daniele
AU - Scartozzi, Mario
AU - Ria, Roberto
AU - Pisconti, Salvatore
AU - Petrelli, Fausto
AU - Vacca, Angelo
AU - Lorusso, Vito
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Metronomic chemotherapy (MC) refers to the close administration of a chemotherapeutic drug for a long time with no extended drug-free breaks. It was developed to overcome drug resistance, partly by shifting the therapeutic target from tumor cells to the tumor vasculature, with less toxicity. Because of this peculiar way of administration, MC can be viewed as a form of long-term 'maintenance' treatment, and can be integrated with standard and conventional chemotherapy in a "chemo-switching" strategy. Additional mechanisms are involved in its antitumor activity, such as activation of immunity, induction of tumor dormancy, chemotherapy-driven dependency of cancer cells, and the '4D effect'. In this paper we report the most important studies that have analyzed these processes. In fact, a number of preclinical and clinical studies in solid tumors as well as in multiple myeloma, have been reported regarding several chemotherapy drugs which have been proposed with a metronomic schedule: vinorelbine, cyclophosphamide, capecitabine, methotrexate, bevacizumab, etoposide, gemcitabine, sorafenib, everolimus and temozolomide. The results of these studies have been sometimes conflicting, highlighting the need to develop reliable tools for patient selection and stratification. However, a more precise evaluation of MC strategies with the ongoing randomized phase II/III clinical is fundamental, because of the strict correlation of this approach with translational research and target therapy. Moreover, because of the low toxicity of MC, these studies will also help to better evaluate the clinical benefit of this treatment, with a special focus on elderly and low performance status patients.
AB - Metronomic chemotherapy (MC) refers to the close administration of a chemotherapeutic drug for a long time with no extended drug-free breaks. It was developed to overcome drug resistance, partly by shifting the therapeutic target from tumor cells to the tumor vasculature, with less toxicity. Because of this peculiar way of administration, MC can be viewed as a form of long-term 'maintenance' treatment, and can be integrated with standard and conventional chemotherapy in a "chemo-switching" strategy. Additional mechanisms are involved in its antitumor activity, such as activation of immunity, induction of tumor dormancy, chemotherapy-driven dependency of cancer cells, and the '4D effect'. In this paper we report the most important studies that have analyzed these processes. In fact, a number of preclinical and clinical studies in solid tumors as well as in multiple myeloma, have been reported regarding several chemotherapy drugs which have been proposed with a metronomic schedule: vinorelbine, cyclophosphamide, capecitabine, methotrexate, bevacizumab, etoposide, gemcitabine, sorafenib, everolimus and temozolomide. The results of these studies have been sometimes conflicting, highlighting the need to develop reliable tools for patient selection and stratification. However, a more precise evaluation of MC strategies with the ongoing randomized phase II/III clinical is fundamental, because of the strict correlation of this approach with translational research and target therapy. Moreover, because of the low toxicity of MC, these studies will also help to better evaluate the clinical benefit of this treatment, with a special focus on elderly and low performance status patients.
KW - Angiogenesis
KW - Bevacizumab
KW - Chemo-switching
KW - Cyclophosphamide
KW - Immunity
KW - Maintenance
KW - Metronomic chemotherapy
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=84930821569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930821569&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2015.01.008
DO - 10.1016/j.critrevonc.2015.01.008
M3 - Article
VL - 95
SP - 46
EP - 61
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
SN - 1040-8428
IS - 1
ER -