Activity of a multitargeted chemo-switch regimen (sorafenib, gemcitabine, and metronomic capecitabine) in metastatic renal-cell carcinoma: a phase 2 study (SOGUG-02-06)

Bellmunt, Joaquim; Trigo, José; Calvo, Emiliano; Carles, Joan; Pérez-Gracia, José Luis; Rubió, J.; Virizuela, Juan Antonio; López, Rafael; Lázaro, M.; Albanell, Joan

doi:10.1016/s1470-2045(09)70383-3

Cited by 60 publications

(34 citation statements)

References 30 publications

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“…Weekly rituximab was combined with four oral antiproliferative oral drugs as metronomic treatment for mantle cell lymphoma [92]. Two clinical trials evaluated the effectiveness of sorafenib when combined with a low dose cytotoxic agent [93,94]. The indications were hepatocellular and renal cell carcinoma.…”

Section: Clinical Studies With Metronomic Chemotherapymentioning

confidence: 99%

Metronomic anti-cancer therapy – an ongoing treatment option for advanced cancer patients

Mross¹,

Neumarkt²

2012

J Cancer Ther Res

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The therapeutic concept of administering agents (cytotoxic/-static,non-cytotoxic and/or targeted drugs) continuously at lower doses -relative to MTDs in the case of cytostatic and cytotoxic drugs or continuously at tolerable doses as in the case of targeted drugs without drug-free breaks over extended periods -known as 'metronomic therapy' (MT), is increasingly being recognized as an experimental option for treating cancer. In comparison with MTD-defined chemotherapy (CHT) regimens, metronomic therapy has demonstrated reduced toxicity. More importantly, several phase II trials have shown that metronomic therapies showed anti-cancer activity in different cancer types with different drugs. The mechanistic basis of metronomic therapy using cytotoxic/static drugs is believed to be primarily anti-angiogenic, either by direct killing or inhibiting endothelial cells (ECs) in the tumor vasculature, killing bone-marrow-derived endothelial progenitor cells, stimulating the immune system, directly affecting tumor cells through a drug-driven effect as well as specificly inhibiting a target when targeting drugs were used in additional to metronomic therapy. The induction of senescence in cancer is another possible explanation for the principles behind 'metronomic therapy' .

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Section: Clinical Studies With Metronomic Chemotherapymentioning

confidence: 99%

Metronomic anti-cancer therapy – an ongoing treatment option for advanced cancer patients

Mross¹,

Neumarkt²

2012

J Cancer Ther Res

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“…60 On the basis of these preclinical studies in the mouse, a phase II study in renal cell carcinoma has been initiated that uses gemcitabine given at its MTD followed by metronomic capecitabine plus the kinase inhibitor sorafenib (that inhibits both VEGFR and PDGFR), and this regimen has shown promising results. 61 Similar experiments performed in the same mouse model have shown that inhibition of cathepsin proteases (proteolytic enzymes that are often found overexpressed at the invasive edges of tumors) in combination with the chemotherapy-switch CTX regimen led to a reduced tumor burden and increased survival.…”

Section: Improving the Effectiveness Of Standard Chemotherapymentioning

confidence: 84%

How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

Politi

Pao

2011

JCO

103

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Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review.

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“…The Spanish Oncology Genitourinary Group (SOGUG)-02-06 phase II trial studied the combination of sorafenib, gemcitabine, and metronomic capecitabine [ 38 ]. Forty treatment-naïve patients with metastatic clear cell RCC were given intravenous gemcitabine (1,000 mg/m 2 on days 1 and 8), oral capecitabine (500 mg/m 2 twice daily on days [1][2][3][4][5][6][7][8][9][10][11][12][13][14], and sorafenib (400 mg twice daily on days 1-21) for six cycles, followed by sorafenib monotherapy.…”

Section: Sorafenib and Chemotherapy Combinationmentioning

confidence: 99%

First-Generation Tyrosine Kinase Inhibitors: Clinical Results

Wong

Eisen

2014

Renal Cell Carcinoma

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Activity of a multitargeted chemo-switch regimen (sorafenib, gemcitabine, and metronomic capecitabine) in metastatic renal-cell carcinoma: a phase 2 study (SOGUG-02-06)

Cited by 60 publications

References 30 publications

Metronomic anti-cancer therapy – an ongoing treatment option for advanced cancer patients

Metronomic anti-cancer therapy – an ongoing treatment option for advanced cancer patients

How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

First-Generation Tyrosine Kinase Inhibitors: Clinical Results

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