RU2347546C1 - Method for prevention of metastasis in case of choroid melanoma fast regression after photodynamic therapy - Google Patents

Abstract

FIELD: medicine; ophthalmology.

SUBSTANCE: after one day and after one month have elapsed since photodynamic therapy of choroids melanoma, antiangiogenic preparation is introduced intravitreally.

EFFECT: complete resorption of angiomatosis tumor, absence of relapses in distant postsurgical period.

2 cl, 1 ex

Description

The invention relates to medicine, and more specifically to ophthalmology, and can be used to prevent metastasis during rapid regression of large and medium hypervascular choroid melanomas after photodynamic therapy,

At the present stage of development of ophthalmic oncology, preference is given to organ-preserving methods of treating choroid melanoma (MX), among which transpupillary photodynamic therapy (PDT) is promising.

After PDT, the tumor regresses rather quickly. So, for example, the case is known when, as a result of PDT, the proinence of choroid melanoma from 7.2 mm decreased to 1.6 mm within 3 months (Yu.A. Bely, M.A. Kaplan, A.V. Tereshchenko, P. L. Volodin, VV Teshchin. Multistage photodynamic therapy of choroid melanoma // Ophthalmology. - 2007. - T. 4. - No. 1. - P.18-24).

However, it has been proved that the balance between pro- and anti-angiogenic factors that inhibits metastasis can only be maintained if the tumor regresses slowly. Against the background of a slow decrease in the main tumor mass, the level of production of pro- and anti-angiogenic factors gradually gradually fades. Otherwise, pro-angiogenic factors are reproduced. This creates favorable conditions for the formation of secondary metastatic nodes (G. G. Ziangirova, V. G. Likhvantseva. Tumors of the vascular tract of the eye. - M., 2001. - P. 160-217; Zimermann LE, McLean IW The Manschot-van Peperzeel concept of the growth and metastasis of uveal melanomas. // Br. J. Ophthalmol. - 1980 - vol. 62 - p. 420).

Therefore, it is necessary to look for ways to prevent metastasis during rapid regression of choroid melanoma, including after transpupillary PDT.

The authors do not know how to prevent metastasis during rapid regression of choroid melanoma after photodynamic therapy.

The objective of the invention is to develop a method for the prevention of metastasis during rapid regression of choroid melanoma after photodynamic therapy.

The technical result of the proposed method is the absence of metastasis in the long term after conducting transpupillary PDT of large and medium hypervascular choroid melanomas.

The technical result is achieved by the fact that after one day and one month after PDT, an antiangiogenic drug, for example avastin, 1.25 mg is intravitreal administered to the patient.

Avastin (bevacizumab) is a recombinant hypercimeric (humanized, close to human) monoclonal antibody that selectively binds to and neutralizes biologically active vascular endothelial growth factor (VEGF).

The technical result is achieved due to the fact that: avastin inhibits the binding of vascular endothelial growth factor to its receptors on the surface of endothelial cells, which leads to a decrease in vascularization and inhibition of tumor growth; administration of avastin suppresses the metastatic progression of the disease and reduces microvascular permeability.

Carrying out photodynamic therapy (PDT) in the first hours and days causes an inflammatory reaction, accompanied by whitening and edema of the retina (Radouil Tzekov, Ton Lin, Kai-Ming Zhang et al. Ocular changes after photodynamic therapy // Invest Ophthalmol Vis Sci. 2006; 47: 377-385), which is a response to laser-induced photochemical tissue damage (Pathology: manual / Ed. By M.A. Paltsev. - M., 2002. - P.90). Further development of the inflammatory reaction leads to the growth of newly formed vessels (Pathology: guidance / Ed. By M.A.Paltsev. - M., 2002. - S.99), which increases the risk of tumor cell migration, and therefore metastasis. In the claimed invention, the first intravitreal injection of an antiangiogenic drug (one day after PDT) is aimed at suppressing the inflammatory reaction and its consequences, since it is proved that already 24 hours after exposure to antiangiogenic therapy, blood supply decreases and the lumen of the newly formed blood vessels decreases, retraction and fragmentation of endothelial are noted cell death by apoptosis mechanism (Inai T, Mancuso M, Hashizume et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. // Am. J. Pathol. 2004, Jul; 165 (1): 35-52).

The second intravitreal injection of an antiangiogenic drug (one month after PDT) is aimed at enhancing scarring processes (Reinier O. Schlingemann. Angiogenesis and fibrosis in age-related macular degeneration and proliferative retinopathy // 8th Euretina congress: European vitreoretinal update 2008. Vienna, Austria, 2008. - P.3: 6), which prevent distant metastasis after transpupillary PDT by replacing the remaining cells with connective tissue (Pathology: manual / Ed. By M.A.Paltsev. - M., 2002. - C .one hundred).

The method is as follows.

One day and one month after PDT, an antiangiogenic drug, for example, avastin, 1.25 mg is intravitreal administered to the patient.

The invention is illustrated by the following data.

Clinical example. Patient I., 59 years old, was admitted to the Kaluga branch of the Federal State Institution IRTC “Eye Microsurgery” in April 2005 with a diagnosis of choroid melanoma (MX) of the right eye.

Visual acuity upon admission to the affected eye was 0.01 with improper light projection.

An ophthalmoscopically in the central zone of the fundus was determined by a heterogeneous gray-yellow irregularly sharpened focus in the vitreous body. On the fluorescence fundus angiogram in the area of formation, characteristic heterogeneous (“spotted”) hyperfluorescence was observed, which confirmed the diagnosis (MX). According to ultrasound data (seroscale B-scan), the size of the neoplasm was 12.8 by 10.9 mm at the base, height - 7.2 mm; according to color and energy Doppler mapping - hypervascular type of blood supply. Above the area of formation, flat exudative retinal detachment was determined.

Informed consent was obtained from the patient to conduct photodynamic therapy of choroid melanoma, followed by intravitreal administration of avastin according to the proposed method.

The observation period is 2.5 years. There were no signs of continued growth, relapse of the neoplasm and metastasis.

The proposed method was applied in 4 patients with large and medium hypervascular choroid melanomas. Duration of observation - from 1.5 to 3 years. In all cases, signs of continued growth, relapse of tumors and metastasis were not detected.

Thus, the proposed method ensures the absence of metastasis in the long term after PDT of large and medium hypervascular choroid melanomas.

Claims (2)

1. A method for the prevention of metastasis during rapid regression of choroid melanoma after photodynamic therapy, which consists in the fact that one day and one month after photodynamic therapy of choroid melanoma, an antiangiogenic drug is intravitreal administered. 2. The method according to claim 1, characterized in that avastin, 1.25 mg, is administered intravitreal as an anti-angiogenic drug.