Prognostic Factors of Metastatic Renal Cell Carcinoma After Failure of Immunotherapy: New Paradigm From a Large Phase III Trial With Shark Cartilage Extract AE 941

Escudier, Bernard; Choueiri, Toni K.; Oudard, Stéphane; Szczylik, Cezary; Négrier, Sylvie; Ravaud, Alain; Chevreau, Christine; Venner, Peter; Champagne, Pierre; Croteau, David; Dupont, Éric; Hariton, C.; Bukowski, Ronald M.

doi:10.1016/j.juro.2007.07.035

Cited by 55 publications

(22 citation statements)

References 15 publications

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“…In our study, the temporal presentation of metastases also remained as the highest significant variable influencing the survival of mCCRCC patients. This finding has also been detected by different authors, although they describe this variable under different names, such as time from initial diagnosis in mCCRCC patients [24], time to nephrectomy to mCCRCC [25] or time from diagnosis to metastatic disease [26]. In this series, the expression of both FAPp and FAPm was positive in more than 80% of synchronous metastases, whereas it was negative in most metachronous lesions.…”

Section: Discussionsupporting

confidence: 76%

“…As previously described in other cancers [11], most mCCRCCs metastasizing into the lymph nodes were FAP positive. These results suggest an early migration of cancer cells from FAP positive primary tumors to lymph nodes, and could explain, at least in part, both the shorter survival outcome of mCCRCC with lymph node metastases [19,26] and also the relationship between FAP expression and worse prognosis of mCCRCC patients.…”

Section: Discussionmentioning

confidence: 99%

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The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases

et al. 2016

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Clear cell renal cell carcinoma (CCRCC) is a heterogeneous and complex disease that frequently develops distant metastases. Fibroblast activation protein (FAP) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with higher risk of metastases and poor survival. The objective of this study was to evaluate the role of FAP in metastatic CCRCC (mCCRCC). A series of 59 mCCRCC retrospectively collected was included in the study. Metastases developed either synchronous (n = 14) or metachronous to renal disease (n = 45). Tumor specimens were obtained from both primary lesion (n = 59) and metastases (n = 54) and FAP expression was immunohistochemically analyzed. FAP expression in fibroblasts from primary tumors correlated with FAP expression in the corresponding metastatic lesions. Also, primary and metastatic FAP expression was correlated with large tumor diameter (>7cm), high grade (G3/4), high stage (pT3/4), tumor necrosis and sarcomatoid transformation. The expression of FAP in primary tumors and in their metastases was associated both with synchronous metastases and also with metastases to the lymph nodes. FAP expression in the primary tumor was correlated with worse 10-year overall survival. Immunohistochemical detection of FAP in the stromal tumor fibroblasts could be a biomarker of early lymph node metastatic status and therefore could account for the poor prognosis of FAP positive CCRCC.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases

et al. 2016

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“…Ultimately, in phase III trials, when coupled with standard chemotherapy, Neovastat had no additive effect on the improvement of overall survival in patients with unresectable stage III non-small cell lung cancer (55). Neovastat has had limited success in the treatment of renal cell carcinoma (56).…”

Section: Discussionmentioning

confidence: 99%

Matrilin-1 Is an Inhibitor of Neovascularization

Foradori

Chen

Fernández

et al. 2014

Journal of Biological Chemistry

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Background:The relative avascularity of cartilage has made it a promising source of angiogenesis inhibitors. Results: MATN-1, identified by mass spectrometry, suppresses capillary endothelial cell proliferation and migration. Conclusion: MATN-1 is a novel inhibitor of neovascularization in vivo and in vitro.Significance: This is the first demonstration that MATN-1 is an inhibitor of both normal and pathological neovascularization.

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“…We performed tumor assessments with CT or MRI on every day 28 of cycles 1–8, and every two cycles thereafter until the end of treatment. Risk group stratification with survival factors was based on other studies [12,13,14]. …”

Section: Methodsmentioning

confidence: 99%

Sunitinib for Asian Patients with Advanced Renal Cell Carcinoma: A Comparable Efficacy with Different Toxicity Profiles

et al. 2011

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Objective: We aimed to describe the efficacy and safety of sunitinib in unselected Korean advanced renal cell carcinoma (RCC) patients. Patients and Methods: From November 2005 to August 2008, 132 histologically confirmed advanced RCC patients (100 in the global expanded access program) were enrolled. Response and toxicity were assessed regularly according to the protocol. Results: Within this population, 82.6% had clear cell RCC, and 28.8% were treatment naïve. Patients received a median of 5 cycles of sunitinib (range 1–30), and the mean relative dose intensity was 82.0 ± 14.20 (SD). The progression-free survival (PFS) and overall survival rates were 8.2 and 23.1 months, respectively. For the 130 evaluable patients, the objective response rate was 34.1% (n = 45); 44.7% (n = 59) exhibited stable disease. Reasons for discontinuation were disease progression (75.0%) and toxicity (7.6%). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), and anemia (69.7%). Low body surface area (OR = 4.2, 95% CI 1.2–13.8, p = 0.02) and previously treated status (OR = 3.1, 95% CI 1.3–7.4, p = 0.01) were highly predictive of grade 3–4 toxicities. Based on these findings, a nomogram predicting the probability of 12-month PFS was constructed, giving a concordance index of 0.675. Conclusions: Despite the different toxicity profiles, maintaining adequate dose modifications and a careful follow-up enables comparable treatment outcomes for unselected Korean advanced RCC patients.

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Prognostic Factors of Metastatic Renal Cell Carcinoma After Failure of Immunotherapy: New Paradigm From a Large Phase III Trial With Shark Cartilage Extract AE 941

Cited by 55 publications

References 15 publications

The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases

The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases

Matrilin-1 Is an Inhibitor of Neovascularization

Sunitinib for Asian Patients with Advanced Renal Cell Carcinoma: A Comparable Efficacy with Different Toxicity Profiles

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