Administration Of Angiogenesis Inhibitor Research Articles

The importance of urine protein-to-creatinine ratio in elderly patients receiving angiogenesis inhibitors

BackgroundPatients receiving angiogenesis inhibitor treatment require attention regarding proteinuria. Monitoring proteinuria using the urine protein-to-creatinine ratio (UPCR) is critical. However, the utility of the UPCR for administering angiogenesis inhibitors to elderly patients remains unclear.ObjectivesWe retrospectively examined whether UPCR measurements are associated with improved efficacy and safety of angiogenesis inhibitors in elderly patients.MethodsThis study included patients who experienced grade 2 or higher proteinuria at least once after the administration of angiogenesis inhibitors. The UPCR values at which bevacizumab and ramucirumab could be administered were defined to be less than 3.5 and 2.0, respectively. The actual total dose/planned total dose was used as an efficacy indicator. A proteinuria rate of grade 2 or higher was used as a safety indicator.ResultsThere were 14 patients in both the UPCR and qualitative test groups. The medians of the actual total dose/planned total dose (%) for the angiogenesis inhibitors in the UPCR and qualitative test groups were 96.8 (48.5–103.9) and 77.7 (9.1–93.1), respectively, with that in the UPCR group being significantly higher (p < 0.001). However, one patient in the UPCR group developed nephrotic syndrome.ConclusionsMonitoring UPCR in elderly patients with grade 2 or higher proteinuria increases the total dosage of angiogenesis inhibitors, which may enhance their therapeutic effects. However, nephrotic syndrome was not fully confirmed in this small-scale study. Although further safety verifications are needed, our findings highlight the importance of monitoring UPCR to improve the efficacy and safety of angiogenesis inhibitors in elderly patients.

Комбинированный подход к лечению хориоидальной неоваскуляризация у пациентов с хронической формой центральной серозной хориоретинопатии

Purpose. To evaluate the effectiveness of combined treatment of chronic central serous chorioretinopathy (CCSCRP) complicated by 1st type choroidal neovascularization (CNV), using subthreshold micropulse laser exposure (SMILV) on the retina and intravitreal administration of angiogenesis inhibitors (IAOAI). Material and methods. In the period from 2017 to 2019, 37 patients (20 men and 16 women) with monolateral chronic recurrent CCSCRP complicated with CNV 1st type, were observed at the Kaluga branch of the S. Fyodorov Eye Microsurgery Federal State Institution. The aged of patients were from 35 to 57 years. In the main group were included 22 patients (22 eyes). In the main group, the anti-VEGF drug was injected once at the initial stage of treatment. During the follow-up examination before the next injection, while the detachment of the neurosensory retina persisted, the patients were immediately transferred to the combination therapy (SMILV + IAOAI). 15 patients (15 eyes) were included in the control group, whose treatment was started with 5 loading doses of the anti-angiogenic drug with an interval of 4 weeks. Results. In the main group, the number of IAOAI varied from 5 to 8 (6.1 ± 0.8). After a single injection of an angiogenesis inhibitor, a positive result was achieved in 3 cases (14%). These patients were performed two additional IAOAI with an interval of 4 weeks, then the interval was increased to 8 weeks. 19 patients (86%) had the detachment of the neurosensory retina with a height of 135-252 µm (177±28.2 µm). SMILV followed by IAOAI was performed for these patients. During the year of observation, from 8 to 10 injections of the inhibitor (8.8 ± 0.77) were performed in the control group of the study. The positive effect after injections of the anti-VEGF drug for 5 months was achieved only in 6 cases (42%). Conclusion. The proposed combination of laser exposure followed by the administration of an angiogenesis inhibitor is effective and can be used as an alternative and safe treatment for 1st type choroidal neovascularization in patients with chronic cerebrovascular accident. Key words: choroidal neovascularization, chronic central serous chorioretinopathy, intravitreal administration of angiogenesis inhibitors, subthreshold micropulse laser exposure.

Intravitreal administration of angiogenesis inhibitor in the treatment of age-related macular degeneration of the retina

Summary: Age related macular degeneration of the retina is a leading cause of severe loss of central vision among elderly people. The introduction into clinical practice of inhibitors of vascular endothelial growth factor has become an important milestone in the treatment of this disease. The article demonstrates three cases of aflibercept (Eylea) application in elderly patients with wet age-related macular degeneration. The medication has demonstrates a high clinical efficacy. Further obser‑ vation is required to assess long-term results.

Сomparative Analysis of the Long-Term Results of Diabetic Macular Edema and Epiretinal Membrane Surgical Treatment

The purpose of the study — to conduct a comparative analysis of structural and functional indicators of the central zone of the retina in patients with diabetic macular edema and epiretinal membrane in the remote period after surgical treatment. Patients and Methods. We examined 97 patients with diabetic macular edema in combination with the epiretinal membrane aged 53 to 68 years (mean age 61 ± 5.4 years). All patients underwent vitrectomy with an internal limiting membrane peeling (ILM). Patients were divided into 3 groups depending on the intravitreal use of an angiogenesis inhibitor. The analysis of the remote anatomical and functional results of patients of different groups during 1 year of observation was carried out. Results. In patients after treatment using the proposed technique, the central retinal thickness was reduced by 16.19 % (p = 0.031) compared with monotherapy and by 11.51 % (p = 0.039) compared with a phased treatment method. Visual acuity significantly increased in the treatment group by the single-step method by 1.53 times (p = 0.024) compared with the group where only vitrectomy was performed, and also 1.44 times (p = 0.029) compared with the delayed administration of angiogenesis inhibitor in avital eye. Patients in all groups have showed an improvement in central photosensitivity 1 month after surgery, followed by a slight decrease in performance. However, by 12 months, the level of central photosensitivity in group 2 was significantly higher than in other groups (p &lt; 0.05). A comparative analysis of the spatial distribution of macular pigment has showed that, along with the development of the pathological process, macular pigments were dispersed in the retinal tissue. On the background of treatment, their concentration was normalized in the central zone of the retina, without increasing the quantitative composition. Conclusion Analysis of the morphofunctional parameters of the retina central section in patients with diabetic macular edema and epiretinal membrane in the dynamics of treatment with various techniques led to the creation of an algorithm for managing patients. It allows to achieve high clinical and functional results in an overwhelming percentage of cases and, thereby, significantly improve medical and social rehabilitation, and also the quality of life of this contingent.

Increased efficacy of stereotactic ablative radiation therapy after bevacizumab in lung oligometastases from colon cancer.

Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months' follow-up after SABR; presence of KRAS mutation. The results were compared with those of a similar cohort of patients with irradiated lung lesions from colorectal cancer in whom bevacizumab was not previously administered. A total of 40 lung metastases were analyzed. The complete response rate after SABR was higher in patients who had received bevacizumab than in those who had not (p = 0.04). Additionally, in the bevacizumab group, a higher rate of post-SABR complete response was observed in case of oligopersistent versus oligorecurrent metastases (p = 0.001). In the setting of lung oligometastases from colon cancer the present study attested the higher efficacy of SABR after bevacizumab administration. Further studies in this field of research are strongly advocated.

Effectiveness of sub-tenon’s administration of an angiogenesis inhibitor in treatment of wet age-related macular degeneration

Aim. To study the clinical results of the administration of an angiogenesis inhibitor into sub-Tenon’s space on the viscous carrier.Methods. The study was conducted in two stages. At the first stage, analysis of examination and treatment of 32 patients (34 eyes) with the wet age-related macular degeneration was conducted. Patients were injected the angiogenesis inhibitor (bevacizumab 12.5 mg) on the viscous carrier (1.0 ml of 2% hydroxypropylmethylcellulose solution) into the posterior sub-Tenon’s space. At the second stage, a retrospective analysis of the treatment results of 30 patients (30 eyes) with the wet age-related macular degeneration, who received the standard monotherapy in the form of 3 monthly intravitreal injection of angiogenesis inhibitor (0.5 mg ranibizumab), and then according to indications, was conducted. The best-corrected visual acuity and optical coherence tomography data over the period of 12 months were evaluated.Results. When comparing the effectiveness of treatment, the mean best-corrected visual acuity significantly improved in both groups after treatment, and its final values were not significantly different. Also central retinal thickness, length, height and volume of lesions significantly decreased as a result of the treatment, and final values were not significantly different between the groups. The duration of the achieved clinical effect in sub-Tenon’s administration was 2-2.5 months, in intravitreal administration - 1-1.5 months.Conclusion. Administration of angiogenesis inhibitors into the posterior sub-Tenon’s space in wet age-related macular degeneration has an equivalent effectiveness to intravitreal introduction and at the same time provides more prolonged effect of medications.

Nefropatía tras la administración de inhibidores de la angiogénesis

Nefropatía tras la administración de inhibidores de la angiogénesis

Effets vasculaires et rénaux des médicaments anti-angiogéniques : recommandations françaises pour la pratique (SN, SFHTA, APNET, FFCD)

Angiogenesis inhibitor drugs (bevacizumab, sunitinib, sorafénib...) are now widely used for treatment of cancers, including colorectal, advanced renal cell and hepatocellular carcinomas, breast cancer). Vascular and renal side-effects of these drugs are not well known. Hypertension is one of the most common side effects. Incidence of hypertension may be different among angiogenis inhibitors and seems dose-depend. Arterial pressure can usually be controlled with anti-hypertensive medications, and treatment with angiogenesis inhibitors can be continued in most cases; however, serious hypertension-induced side effects were reported included malignant hypertension, stroke and reversible posterior leucoencephalopathy. Renal damage is infrequently reported: usually reversible mild or moderate proteinuria and in some rare cases nephritic syndrome, acute renal dysfunction, proliferative or collapsing glomerulonephritis, interstitial nephritis and thrombotic microangiopathy. Prolongation of the QT interval, congestive heart failure and left ventricular dysfunction have been reported in patients using tinibs. In the present guidelines, we recommend: (1) before the first administration of angiogenesis inhibitors: acute IV or oral antihypertensive medications should not be administered in a patient regardless of arterial pressure levels with postponing the administration because of hypertension is not recommended; (2) initial work-up should include ambulatory measurement of arterial pressure (by the general practitioner or by the patient using home blood pressure (three times in the morning and in the evening during three consecutive days) with a validated (cf: http://afssaps.sante.fr/) upper arm device: ideally, this device should be financed and provided by the pharmaceutical companies marketing the angiogenesis inhibitor drugs. Using 24-hour ambulatory blood pressure measurement is optional; (3) urine dipstick (and quantification if positive) and estimated glomerular filtration rate (using abbreviated MDRD rather than Cockcroft-Gault formula) must be performed before treatment and regularly during follow-up; (4) therapeutic management must be done in accordance with national or international guidelines (in France: http://www.has-sante.fr/); (5) optimal care is best achieved within a network of professionals including general practitioners, oncologists, cardiologists and nephrologists.

Cancer gene therapy targeting angiogenesis: An updated Review

Since the relationship between angiogenesis and tumor growth was established by Folkman in 1971, scientists have made efforts exploring the possibilities in treating cancer by targeting angiogenesis. Inhibition of angiogenesis growth factors and administration of angiogenesis inhibitors are the basics of anti-angiogenesis therapy. Transfer of anti-angiogenesis genes has received attention recently not only because of the advancement of recombinant vectors, but also because of the localized and sustained expression of therapeutic gene product inside the tumor after gene transfer. This review provides the up-to-date information about the strategies and the vectors studied in the field of anti-angiogenesis cancer gene therapy.

Delay in administration of CDDP until completion of AGM-1470 treatment enhances antimetastatic and antitumor effects.

The efficacy of cis-diammine dichloroplatinum (CDDP) therapy in combination with continuous administration of angiogenesis inhibitor o-(chloroacetyl-carbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transplantable rat osteosarcoma line previously established in our laboratory. AGM-1470 (2.5 mg/kg body weight/week) was administered by Alzet osmotic pumps for 2 weeks starting from 7 days after tumor inplantation and CDDP (1.25 mg/kg) was given on days 21 and 24. The number of lung metastatic nodules was counted and the wet weights of the primary tumors were measured 5 weeks after tumor inplantation. Values with administration of CDDP 3 days after discontinuation of AGM-1470 were significantly lower than when the two agents were coadministered (P < 0.05). This animal model should facilitate optimization of the timing of combination therapy.