A phase II study of gemcitabine (G) and capecitabine (C) in patients with metastatic renal cell cancer (mRCC): A report of Cancer and Leukemia Group B #90008

Stadler, Walter M.; Halabi, Susan; Ernstoff, Marc S.; Barrier, Robert; Davila, Evelyn P.; Picus, Joel; Small, Eric J.

doi:10.1200/jco.2004.22.90140.4515

Cited by 19 publications

(22 citation statements)

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“…Single-agent regimens have shown response rates of 5-6 % in trials involving over 4,000 cases and more than 30 individual agents (Motzer et al 2000;Yagoda et al 1995). 5-fluorouracil and gemcitabine combinations have yielded slightly better response rates (10-15 %) (Rini et al 2005;Stadler et al 2006).…”

Section: Chemotherapymentioning

confidence: 98%

The Role of Inflammation in Kidney Cancer

Chevez

Finke

Bukowski

2014

Advances in Experimental Medicine and Biology

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Renal cell carcinoma (RCC) constitutes more than 90 % of primary kidney tumors with the development of metastatic disease in the lung, bone, liver, and brain. Clear-cell RCC (CCRCC) is the most common histologic form of sporadic kidney cancer where the majority of tumors have inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene resulting in the accumulation of hypoxia-inducible factor (HIF) leading to dysregulation of cell growth and angiogenesis. Understanding of the genetic changes in RCC and the downstream events have led to the development of tyrosine kinase inhibitors (TKI) that target HIF-regulated proteins which currently represents front-line therapy for metastatic disease although resistance develops in most patients overtime. Despite the fact that RCC is an immunogenic tumor, there is mounting evidence that immune cells and inflammatory pathways can enhance tumor growth and immune escape. However, recent studies are beginning to uncover the mechanisms of immune escape in RCC, and the role inflammatory immune cells and cytokines play is this process. These new findings have led to renewed interest in the use of immunotherapy for the treatment of this disease that includes strategies to regulate inflammatory responses. Here, we will discuss the different inflammatory signaling pathways (e.g., VHL, hypoxia, TNF-α, STAT, and TGF-β) and the downstream transcription factors, cytokines, and chemokines involved in tumor development, and disease progression. This will include assessment of the role inflammatory molecules (e.g., pVHL, TGFb, IL6, select chemokines/chemokine receptors) play in promoting cell transformation, survival, proliferation of tumor cells, and metastasis derived from in vitro and in vivo studies. Included is a section on how select inflammatory cells (TAM, MDSC, and neutrophils) promote tumor evasion of immune cells. We also provide examples of molecules/cells that correlate negatively (CXCL12, CXCR4, and MMP, neutrophils, and MDSC) and positively (TH1 cells, IP-10, and MIG) with tumor progression and survival. Finally, there is a discussion of different inhibitors of inflammation that may be useful in the treatment of RCC.

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Section: Chemotherapymentioning

confidence: 98%

The Role of Inflammation in Kidney Cancer

Chevez

Finke

Bukowski

2014

Advances in Experimental Medicine and Biology

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“…Gemcitabine in combination with doxorubicin or capecitabine has shown some activity in patients with non-clear cell or clear cell tumors with sarcomatoid features. [186][187][188][189][190][191] The potential role of sunitinib in combination gemcitabine has been investigated in a phase II trial of RCC with sarcomatoid features. 192 Results show that the combination is well tolerated and active, especially in patients with rapidly progressing disease.…”

Section: Chemotherapy For Metastatic Rccmentioning

confidence: 99%

Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Motzer¹,

Jonasch²,

Agarwal³

et al. 2017

J Natl Compr Canc Netw

517

516

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“…Metastatic RCC is generally resistant to standard chemotherapy, radiotherapy and hormonal therapy. Objective response rates (ORR) of <10% have been reported with frequently used chemotherapeutic agents (gemcitabine, fluorouracil, capecitabine, vinblastine) [7] and combination treatment with gemcitabine plus capecitabine in 60 patients with metastatic RCC was associated with an ORR of 15% [8].…”

Section: Introductionmentioning

confidence: 99%

Treatment options in renal cell carcinoma: past, present and future

Oudard¹,

George²,

Médioni³

et al. 2007

Annals of Oncology

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Cytokine therapies have been the standard of care in metastatic renal cell carcinoma (RCC). However, these agents only provide clinical benefit to a small subset of patients and are associated with significant toxicity. A better understanding of the molecular biology of RCC has identified the vascular endothelial growth factor (VEGF) and platelet-derived growth factor signalling pathways as rational targets for anticancer therapy. The multitargeted receptor tyrosine kinase inhibitors sunitinib and sorafenib have both demonstrated improved efficacy as second-line therapy in patients with RCC. Sunitinib has also been shown to be effective in the firstline setting, and has recently received European Union approval as first-line treatment for advanced and/or metastatic RCC. There is also recent evidence that temsirolimus (an inhibitor of the mammalian target of rapamycin) and bevacizumab (a mAb targeted against VEGF) may provide benefits in the first-line treatment setting. These results confirm that inhibiting these tumour targets is a feasible approach to treatment and provides a more positive outlook for the future management of metastatic RCC.

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A phase II study of gemcitabine (G) and capecitabine (C) in patients with metastatic renal cell cancer (mRCC): A report of Cancer and Leukemia Group B #90008

Cited by 19 publications

References 0 publications

The Role of Inflammation in Kidney Cancer

The Role of Inflammation in Kidney Cancer

Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Treatment options in renal cell carcinoma: past, present and future

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