Distinct cytokines predict response to immunotherapy and targeted therapy in metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 352-352
Author(s):  
Alex Chehrazi-Raffle ◽  
Luis A Meza ◽  
Marice Alcantara ◽  
Nicholas Salgia ◽  
Nazli Dizman ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Vascular Endothelial ◽  
Protein Assay ◽  
Ongoing Work ◽  
Plasma Cytokines ◽  
A Prospective Study ◽  
Endothelial Growth Factor ◽  
To Receive

352 Background: Previous studies have suggested a link between plasma cytokines and mRCC outcomes with systemic therapy. In a prospective study, we assessed whether plasma cytokines could separately predict outcome with immunotherapy or targeted therapy. Methods: Eligible patients (pts) had histologically proven mRCC with intent to receive a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or an immune checkpoint inhibitor (ICI). Immunologic profiles were evaluated at several time points using a Human Cytokine 30-plex protein assay (Invitrogen). Clinical benefit (CB) was defined as complete response, partial response, or stable disease ≥ 6 months. Results: A total of 56 pts (40:16 M:F) were enrolled; 23 pts and 33 pts received VEGF-TKI and ICI, respectively. The most common VEGF-TKI was cabozantinib; the most common ICI was nivolumab. CB was similar between VEGF-TKI and ICI arms (65% vs 54%). Pts with CB from VEGF-TKIs had lower pretreatment levels of IL-6 (p = 0.02), IL-1RA (p = 0.03), and G-CSF (p = 0.02). Major shifts in plasma cytokines were seen as early as one month; these data will be presented. Conclusions: Distinct plasma cytokines predict benefit with VEGF-TKIs and ICIs. Ongoing work will incorporate analysis of pts receiving VEGF-TKI and ICI combination therapy.

Final results of a phase Ib study of tivozanib and FOLFOX6 in patients (pts) with advanced gastrointestinal (GI) tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4132-4132 ◽  
Author(s):  
Ferry Eskens ◽  
Corina N. Oldenhuis ◽  
Walter J. Loos ◽  
Brooke Esteves ◽  
Leni van Doorn ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Tumor Model ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Vascular Endothelial ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Endothelial Growth Factor ◽  
Anti Tumor Activity

4132 Background: Tivozanib is a potent, selective, oral small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 with a long half-life. A Phase I study found tivozanib's maximum tolerated dose (MTD) to be 1.5 mg/d and responses were observed in pts with colorectal cancer (CRC) and other tumors. Tivozanib has shown additive anti-tumor activity with 5-fluorouracil in a preclinical breast tumor model. FOLFOX6 is a standard chemotherapy for GI cancers. This open-label, Phase Ib study (NCT00660153) sought to determine the MTD, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and anti-tumor activity of escalating doses of tivozanib combined with a modified (m) FOLFOX6 regimen (85 mg/kg2 oxaliplatin) in pts with advanced GI tumors. Methods: Tivozanib was administered once daily in 4-week cycles (3 weeks on, 1 week off) with mFOLFOX6 administered on Days 1 and 15 of each cycle. Pts also received a single dose of tivozanib on day -5 for PK analysis. Pts were allowed to continue tivozanib following discontinuation of mFOLFOX6. Results: Twenty two pts (14:8 male:female; median age 58 years; 91% Caucasian) received tivozanib 0.5 mg (n=9), 1.0 mg (n=3), or 1.5 mg (n=10) and mFOLFOX6. Pts received a median of 5.2 (range 0.0 to 25.1) months of treatment. DLTs were observed in 2 pts on tivozanib 0.5 mg (reversible Grade [Gr] 3 diarrhea and Gr 3/4 transaminase elevations) and in 2 pts on tivozanib 1.5 mg (Gr 3 seizure and reversible Gr 3 vertigo). Other Gr 3/4 drug-related adverse events (AEs) included neutropenia, fatigue, and hypertension (n=2 each). Eight pts discontinued treatment due to AEs. The MTD for tivozanib with mFOLFOX6 was 1.5 mg. The disease control rate was 63% (<1% complete response, 27% partial response, 36% stable disease). Preliminary PK data showed no interaction between tivozanib and mFOLFOX6. Eight additional pts enrolled at the 1.5 mg dose level are currently being evaluated. Final results will be presented. Conclusions: Tivozanib can be combined at its recommended dose of 1.5 mg/day with mFOLFOX6 for pts with advanced GI tumors. The combination was tolerable and showed encouraging anti-tumor activity. A Phase II study of this combination for mCRC is ongoing.  

Vascular endothelial growth factor tyrosine kinase inhibitor targeted therapy: a potential cause of an acute aortic dissection lesser known to the emergency physician

2021 ◽  
Vol 14 (10) ◽  
pp. e245653
Author(s):  
Jocelyn Ting ◽  
Zhiwen Joseph Lo
Keyword(s):  
Risk Factors ◽  
Vascular Endothelial Growth Factor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Aortic Dissection ◽  
Tyrosine Kinase Inhibitor ◽  
Acute Aortic Dissection ◽  
Kinase Inhibitor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

A 59-year-old Chinese male presented to the emergency department with acute onset epigastric pain. He had no cardiovascular risk factors and was only on targeted therapy, pazopanib, for newly diagnosed metastatic renal clear cell carcinoma. He was found to have a Stanford type B acute aortic dissection with moderately elevated systolic blood pressure of 150 mm Hg. Although not a listed side effect, various case reports have shown a potential association between the use of vascular endothelial growth factor tyrosine kinase inhibitor targeted therapy and an acute aortic dissection. It would be prudent to consider the possibility of an aortic dissection in patients on such drugs with suspicious clinical presentation, even in the absence of other risk factors.

scholarly journals Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
An Uche ◽  
Chad Sila ◽  
Tad Tanoura ◽  
James Yeh ◽  
Neil Bhowmick ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Heavily Pretreated ◽  
Treatment Paradigm ◽  
Endothelial Growth Factor

Cabozantinib represents an established vascular endothelial growth factor- (VEGF-) tyrosine kinase inhibitor (TKI) in the treatment paradigm of metastatic renal cell carcinoma (mRCC). Its activity in mRCC patients with brain metastases (BMs) has been largely underreported in prospective clinical trials. We present the unique case of a heavily pretreated mRCC patient with BMs who achieved a brain complete response to cabozantinib prior to receiving radiation therapy. We end with a literature review and discussion of the biologic rationale and growing evidence supporting the intracranial activity of cabozantinib.

scholarly journals Alternative chemoradiotherapy in anal carcinoma patients with mutations in thymidylate synthase and dihydropyrimidine dehydrogenase genes

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Muhammad Wasif M. Saif ◽  
Ruchi Hamal ◽  
Nauman Siddiqui ◽  
Antonia Maloney ◽  
Melissa Smith
Keyword(s):  
Dihydropyrimidine Dehydrogenase ◽  
Anal Carcinoma ◽  
Complete Response ◽  
Genetic Mutations ◽  
Molecular Testing ◽  
Severe Toxicity ◽  
Metabolizing Enzymes ◽  
Radiological Response ◽  
A Prospective Study ◽  
To Receive

Background: 5-fluorouracil (5-FU) and mitomycin-C (MMC) with radiotherapy (RT) remain an established treatment for patients with anal cancer (AC). Genetic mutations in two major metabolizing enzymes for 5-FU; dihydropyrimidine dehydrogenase ( DPYD and thymidylate synthetase ( TYMS), have been associated with clinical response and toxicity. However, their place in the treatment of AC remains undetermined. Methods: We retrospectively reviewed 21 patients with AC, including T2-4, N0-1, M0 or T1-4, N2-3, and M0 treated between 2012 and 2018. All patients were treated with 5-FU 1,000 mg/m2/day via continuous intravenous (IV) infusion 1–4 and 29–32, MMC 10 mg/m2 IV bolus days 1 and 29 plus RT. Patients who developed ⩾3 grade toxicities were tested for the DPYD and TYMS genes. Treatment was either modified with reduced doses or changed to MMC 10 mg/m2 day 1 and 29 with cisplatin 25 mg/m2/week plus RT. Toxicities and responses were collected. Results: Six out of 21 patients who developed ⩾3 grade toxicities including pancytopenia, neutropenia, thrombocytopenia, mucositis, nausea, rash, and nephritis were found to have genetic mutations: TYMS 2RG/3RC ( n = 2), 3RG/3RC ( n = 1), 2R/2R ( n = 2), T YMS 3′UTR del/Ins ( n = 2), and DPYD c.2864A > T heterozygous ( n = 1). Two patients received 5-FU at a 50% reduced dose on days 29–32; one patient refused to receive 5-FU (continued with MMC and RT); one patient received only radiation therapy due to persistent pancytopenia despite the use of growth factors; two patients received an alternative regimen consisting of MMC 10 mg/m2 on day 29 with cisplatin (CDDP) 25 mg/m2/week plus RT; and two patients received cisplatin/MMC with RT from the beginning as they were prospectively detected to have TYMS abnormalities prior to dosing the chemotherapy. These patients tolerated treatment very well with only grade 2 toxicities. All the patients (4/4) on cisplatin/MMC achieved clinical complete response (cCR), while four patients (4/15) on 5-FU/MMC reached cCR at the first assessment. Radiological response showed complete response at the end of 24 weeks assessment. Conclusions: Molecular testing for DPYD and TYMS genes can allow us to identify patients who are most likely to respond or face severe toxicity to 5-FU in a potentially curable cancer. Combining radiation with CDDP with MMC in patients with AC is feasible. A prospective study based on pharmacogenetic testing comparing MMC/cisplatin with MMC/5-FU is indicated in patients with AC.

Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis

2021 ◽  
Vol 157 ◽  
pp. 103186
Author(s):  
Avash Das ◽  
Somnath Mahapatra ◽  
Dhrubajyoti Bandyopadhyay ◽  
Santanu Samanta ◽  
Sandipan Chakraborty ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Myopic foveal detachment associated with pachychoroid characteristics

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Kyun Shin ◽  
Sun Hyup Han ◽  
Se Woong Kang ◽  
Sang Jin Kim ◽  
A Young Kim
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Multimodal Imaging ◽  
High Myopia ◽  
Complete Response ◽  
Response To Treatment ◽  
Vascular Endothelial ◽  
Foveal Detachment ◽  
Endothelial Growth Factor ◽  
Choroidal Vascular Hyperpermeability

Abstract Purpose To describe myopic nontractional foveal detachment associated with pachychoroid diseases. Methods This retrospective study included 15 myopic eyes which had nontractional serous foveal detachment. The eyes were divided into myopic central serous chorioretinopathy (CSC) group (n = 8) and a myopic pachychoroid neovascularization (PNV) group (n = 7) according to the presence of type 1 choroidal neovascularization on multimodal imaging. The findings of multimodal imaging and treatment response were described. Results In myopic CSC group, pachychoroid features such as pachyvessels, choroidal vascular hyperpermeability and punctate hyperfluorescent spots were noted in 8 eyes (100%), 8 eyes (100%), 5 eyes (62.5%) respectively. The above features were noted in 7 eyes (100%), 5 eyes (83.3%), 5 eyes (83.3%), respectively, in the myopic PNV group. Five of 8 eyes in myopic CSC and all 7 eyes received treatment including anti-vascular endothelial growth factor injection and/or photodynamic therapy. However, only five eyes had a complete response. Conclusions The pachychoroid phenotype may coexist with high myopia and lead to myopic nontractional serous foveal detachment. Our series suggest that the response to treatment for these conditions would be limited.

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