Pharmacodynamic study of FLT-PET imaging in patients treated with sunitinib

Liu, G.; Jeraj, Robert; Perlman, Scott; Vanderhoek, M; Kolesar, J.; Eickhoff, Jens; Alberti, D.; Wilding, Greg

doi:10.1200/jco.2008.26.15_suppl.3515

Cited by 13 publications

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“…Some patients appreciate the 2-week interruption in sunitinib treatment, and many of the adverse events associated with the treatment are resolved during the “ drug holiday,” including treatment-emergent fatigue [ 52 , 53 ], which allows patients to plan/attend activities and events that they would otherwise be unable to participate in. However, a minority of patients experience tumor flare while off treatment [ 53 , 54 ], which may lead to increased levels of fatigue as a consequence of tumor growth [ 52 ].…”

Section: F Atigue a Ssociated With The mentioning

confidence: 99%

Fatigue in Renal Cell Carcinoma: The Hidden Burden of Current Targeted Therapies

2010

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Section: F Atigue a Ssociated With The mentioning

confidence: 99%

Fatigue in Renal Cell Carcinoma: The Hidden Burden of Current Targeted Therapies

2010

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“…We suspected that this VEGFR TKI withdrawal flare may be associated with a period of rapid, transient tumor re-growth,(20, 21) and that the pain would decrease with resumption of therapy. We suggested that during this “flare,” the tumor would be more engaged in S-phase of the cell cycle (proliferation) and thus more responsive to cytotoxic chemotherapy.…”

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confidence: 99%

Pharmacodynamic Study Using FLT PET/CT in Patients with Renal Cell Cancer and Other Solid Malignancies Treated with Sunitinib Malate

Liu

Jeraj

Vanderhoek

et al. 2011

Clinical Cancer Research

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Purpose To characterize proliferative changes in tumors during the sunitinib malate exposure/withdrawal using 3′-Deoxy-3′-[18F]fluorothymidine (FLT) PET/CT imaging. Patients and Methods Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PET/CT imaging. Sunitinib was initiated at the standard dose of 50 mg PO daily either on a 4/2 or 2/1 schedule. FLT PET/CT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic data were assessed at the same time points. Results 16 patients (8 pts on 4/2 schedule; 8 pts on 2/1 schedule) completed all three planned FLT PET/CT scans, and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scan 2 to 3), median FLT PET SUVmean increased +15% (range −14% to +277%) (p=0.047) for the 4/2 schedule and +19% (range −5.3% to +200%) (p=0.047) for the 2/1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure, and returned towards baseline during the treatment withdrawal. Conclusions The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGFR TKI withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early “angiogenic escape”.

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“…Notably, Sn-dichalcogenides, such as SnS 2 and SnSe 2 , crystallize two-dimensionally into hexagonal unit cells with the Sn oxidation state of +4, to form semiconductors with a large band gap E g 12−14 in which the Sn ions are coordinated to six chalcogen ions in the octahedral sites with space group P3̅ m1 within a monolayer, which is stacked on top of another monolayer by van der Waals interaction without translational displacements (Figure 1a). However, Sn-chalcogenides can also crystallize in orthorhombic unit cells to form 2D Sn-monochalcogenides 15,16 in which Sn ions with oxidation state of +2 are coordinated to three chalcogen ions to form an orthorhombic unit cell with the space group of Pnma, which comprises zigzag double planes of the Sn and chalcogen atoms separated by a van der Waals gap (Figure 1b). In bulk crystal forms, hexagonal SnS 2 and orthorhombic SnS exhibit n-type and p-type semiconductor characteristics, respectively.…”

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Deterministic Two-Dimensional Polymorphism Growth of Hexagonal n-Type SnS₂ and Orthorhombic p-Type SnS Crystals

et al. 2015

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van der Waals layered materials have large crystal anisotropy and crystallize spontaneously into two-dimensional (2D) morphologies. Two-dimensional materials with hexagonal lattices are emerging 2D confined electronic systems at the limit of one or three atom thickness. Often these 2D lattices also form orthorhombic symmetries, but these materials have not been extensively investigated, mainly due to thermodynamic instability during crystal growth. Here, we show controlled polymorphic growth of 2D tin-sulfide crystals of either hexagonal SnS2 or orthorhombic SnS. Addition of H2 during the growth reaction enables selective determination of either n-type SnS2 or p-type SnS 2D crystal of dissimilar energy band gap of 2.77 eV (SnS2) or 1.26 eV (SnS) as a final product. Based on this synthetic 2D polymorphism of p-n crystals, we also demonstrate p-n heterojunctions for rectifiers and photovoltaic cells, and complementary inverters.

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Pharmacodynamic study of FLT-PET imaging in patients treated with sunitinib

Cited by 13 publications

References 0 publications

Fatigue in Renal Cell Carcinoma: The Hidden Burden of Current Targeted Therapies

Fatigue in Renal Cell Carcinoma: The Hidden Burden of Current Targeted Therapies

Pharmacodynamic Study Using FLT PET/CT in Patients with Renal Cell Cancer and Other Solid Malignancies Treated with Sunitinib Malate

Deterministic Two-Dimensional Polymorphism Growth of Hexagonal n-Type SnS₂ and Orthorhombic p-Type SnS Crystals

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Pharmacodynamic study of FLT-PET imaging in patients treated with sunitinib

Cited by 13 publications

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Fatigue in Renal Cell Carcinoma: The Hidden Burden of Current Targeted Therapies

Fatigue in Renal Cell Carcinoma: The Hidden Burden of Current Targeted Therapies

Pharmacodynamic Study Using FLT PET/CT in Patients with Renal Cell Cancer and Other Solid Malignancies Treated with Sunitinib Malate

Deterministic Two-Dimensional Polymorphism Growth of Hexagonal n-Type SnS2 and Orthorhombic p-Type SnS Crystals

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Deterministic Two-Dimensional Polymorphism Growth of Hexagonal n-Type SnS₂ and Orthorhombic p-Type SnS Crystals