Phase <scp>II</scp> trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration‐resistant prostate cancer

Madan, Ravi A.; Karzai, Fatima; Ning, Yang‐Min; Adesunloye, Bamidele; Huang, Xuan; Harold, Nancy; Couvillon, Anna; Chun, Guinevere; Cordes, Lisa; Sissung, Tristan M.; Beedie, Shaunna; Dawson, Nancy A.; Theoret, Marc R.; McLeod, David G.; Rosner, Inger L.; Trepel, Jane B.; Lee, Min-Jung; Tomita, Yusuke; Lee, Sunmin; Chen, Clara; Steinberg, Seth M.; Arlen, Philip M.; Gulley, James L.; Figg, William D.; Dahut, William L.

doi:10.1111/bju.13412

Cited by 27 publications

(19 citation statements)

References 30 publications

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“…Third, the number of subjects and selection bias in our study are potential factors affecting our assessment of the relationship between ADC and VEGF expression level. Anti‐VEGF therapies in clinical studies have shown some benefits for patients with PCa . According to our results, we can speculate that ADC may be used as a biomarker to assess the treatment response to anti‐VEGF drugs in PCa.…”

Section: Discussionsupporting

confidence: 59%

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Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki‐67, HIF‐1α and VEGF

Yang

Jing

et al. 2018

NMR in Biomedicine

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Prostate cancer (PCa) is the second most common cancer in men. The Gleason score (GS) and biomarkers play important roles in the diagnosis and treatment of patients with PCa. The purpose of this study was to investigate the relationship between the apparent diffusion coefficient (ADC) and the molecular markers Ki-67, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in PCa. Thirty-nine patients with 39 lesions, who had been diagnosed with PCa, were enrolled in this study. All patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) (b = 800 s/mm ). The expression of Ki-67, HIF-1α and VEGF was assessed by immunohistochemistry. Statistical analysis was applied to analyze the association between ADC and prostate-specific antigen (PSA), GS and the expression of Ki-67, HIF-1α and VEGF. The group differences in ADC among different grades of Ki-67, HIF-1α and VEGF were also analyzed. The mean ± standard deviation of ADC was (0.76 ± 0.27) × 10 mm /s. ADC correlated negatively with PSA and GS (p < 0.05). The Ki-67 staining index (SI), HIF-1α expression and VEGF expression in PCa were correlated inversely with ADC, controlling for age (r = -0.332, p < 0.05; r = -0.662, p < 0.0005; and r = -0.714, p < 0.0005, respectively). ADC showed a significant difference among different grades of Ki-67 (F = 9.164, p = 0.005), HIF-1α (F = 40.333, p < 0.0005) and VEGF (F = 22.048, p < 0.0005). In conclusion, ADC was correlated with PSA, GS, and Ki-67, HIF-1α and VEGF expression in patients with PCa. ADC may be used to evaluate tumor proliferation, hypoxia and angiogenesis in PCa.

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Section: Discussionsupporting

confidence: 59%

“…Antiangiogenic treatment has been shown to be effective in inhibiting the progression of some tumors. Many recent trials have found that a combination of VEGF inhibitors may have clinical benefits for patients with PCa, and anti‐VEGF therapies are emerging as promising treatment methods for PCa.…”

Section: Introductionmentioning

confidence: 99%

Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki‐67, HIF‐1α and VEGF

Yang

Jing

et al. 2018

NMR in Biomedicine

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“…There are several possible explanations for the failure of these trials, including hetereogeneity in patient stages and selection, treatment-related toxicities or activation of resistance mechanism through induction of pro-angiogenic factors [12] , [13] . A recent phase II trial concludes that combination of anti-angiogenics (bevacizumab and lenalidomide⿿though arguably lenalidomide is not a ⿿pure⿿ anti-angiogenic) is able to circumvent the toxicity and may have clinical benefit [14] . Despite the insufficient data for the effectiveness of anti-angiogenic treatment in PCa, the above mentioned studies suggest that further research is required to establish the exact mechanism of regulation of angiogenesis in tumours.…”

Section: Is There a Rationale For Developing Anti-angiogenics In Prosmentioning

confidence: 99%

SRPK1 inhibition in prostate cancer: A novel anti-angiogenic treatment through modulation of VEGF alternative splicing

Mavrou¹,

Oltean

2016

Pharmacological Research

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“…CD8 + T-cells, Foxp3 − CD4 + T-cells, and Tregs were evaluated for levels of expression of immune checkpoint receptors (CTLA-4, PD-1, and TIM-3). CD14 + monocytes were evaluated for HLA-DR expression, and the levels of CD14 + HLA-DR hi monocytes and CD14 + HLA-DR low/neg monocytes were evaluated as described previously 47 . The following monoclonal antibodies were used (all from BioLegend, San Diego, CA, USA): for MDSC analysis, Alexa Fluor 647-CD3 clone OKT3, Alexa Fluor 647-CD56 clone MEM-188, Alexa Fluor 647-CD19 clone HIB19, PE-Cy7-HLA-DR clone L243, PerCP-CD14 clone HCD14, Alexa Fluor 488-CD11b clone ICRF44, PE-CD33 clone WM53, and Pacific Blue-CD40 clone 5C3.…”

Section: Methodsmentioning

confidence: 99%

The interplay of epigenetic therapy and immunity in locally recurrent or metastatic estrogen receptor-positive breast cancer: Correlative analysis of ENCORE 301, a randomized, placebo-controlled phase II trial of exemestane with or without entinostat

et al. 2016

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Entinostat, a class I-selective histone deacetylase inhibitor, has shown promising activity in ENCORE 301, a randomized, placebo-controlled, phase II trial of exemestane with or without entinostat in women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. ENCORE 301 showed an 8.3-mo improvement in median overall survival among patients who received entinostat. We investigated the impact of entinostat on immune subsets with CD40, HLA-DR, and immune checkpoint receptor expression analyses in 34 patient blood samples from ENCORE 301. We found that entinostat significantly decreased granulocytic and monocytic MDSCs at cycle 1 day 15. MDSC CD40 was significantly downregulated by entinostat. A significant increase in HLA-DR expression on CD14+ monocytes by entinostat was observed. Entinostat did not impact T-cell subsets or T-cell immune checkpoint receptor expression. Our findings suggest that a significant interplay between this epigenetic regimen and host immune homeostatic mechanisms may impact therapeutic outcome.

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Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration‐resistant prostate cancer

Abstract: With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis-generating data would require randomized trials to confirm the findings.

Cited by 27 publications

References 30 publications

Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki‐67, HIF‐1α and VEGF

Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki‐67, HIF‐1α and VEGF

SRPK1 inhibition in prostate cancer: A novel anti-angiogenic treatment through modulation of VEGF alternative splicing

The interplay of epigenetic therapy and immunity in locally recurrent or metastatic estrogen receptor-positive breast cancer: Correlative analysis of ENCORE 301, a randomized, placebo-controlled phase II trial of exemestane with or without entinostat

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