RU2445991C2 - Method of organ-preserving treatment of patients with initial carcinoma of vulva - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, and may be used for organ-preserving treatment of the patients with initial carcinoma of vulva. That is ensured by sequential intravenous introduction of radachlorine and per os administration of alasensl Then the patient is exposed to distant surface laser light of wave length 662 nm, power density 80-150 J/cm² and wave length 630 nm of the same power density with using a quartz light guide. The quartz light guide is provided with a microlens.

EFFECT: method provides an adequate anticancer effect, single-step photodynamic exposure, an organ-preserving effect in women of reproductive age, reduced basic dose within the tumour location, the absence of destructive tissue changes within a photodynamic exposure coverage, reduced length of wound epithelisation, shorter rehabilitation and extended indications in women of various ages.

2 cl, 1 ex

Description

The invention relates to medicine, namely to methods for treating malignant neoplasms by means of photodynamic therapy (hereinafter - PDT), and can be used as an organ-preserving treatment of patients with initial forms of vulvar cancer (PB) by PDT, avoiding surgery.

RV - the diagnosis of women of advanced and senile age. At the same time, this pathology is diagnosed not only in patients of this age group, but also more often in the reproductive age, which necessitates the search for new organ-preserving treatment methods alternative to traditional ones.

One of the newest approaches to the treatment of vulvar pathology is PDT. The general concept of the use of PDT in the treatment of RV is determined by the clinical stage of the disease, the localization of the process, the morphological structure of the tumor, the somatic state of a particular patient.

There is a method of treating RV with the drug Photosens in patients with an exophytic or more often endophytic tumor location (T1-2N0M0), the histological form of which was different: squamous keratinizing cancer, squamous non-keratinizing cancer, Paget cancer, glandular cancer, basal cell cancer (Zangieva F.A. // Laser fluorescence diagnostics and PDT of vulvar cancer. Diss. For the degree of candidate of medical sciences 2005). In accordance with the known method, Photosens was administered at a dose of 0.5 mg / kg 24 hours before PDT. The dose of the energy density of one light spot was 150-300 J / cm ² , the total dose for multipolar irradiation was 200-800 J / cm ² , the radiation power density was 200-250 mW / cm ² . One to three PDT sessions were performed during the course of treatment. The treatment procedure was more or less painful for most patients. In addition, the disadvantages of this technique is the use of a physical treatment method without taking into account the localization and prevalence of the tumor process, which can very likely lead to relapse of the tumor.

Closest to the claimed invention, a method of the same purpose is a method of treating patients with RV 1-2a-3a stage by PDT with the Photosens drug for superficial cancers and in cases of solid and exophytic tumors (RU No. 2296597). Adopted as a prototype. In accordance with the prototype method, in the first stage of treatment by means of a high-energy CO ₂ laser, the main tumor was simultaneously excised within healthy tissues or the maximum possible cytoreductive surgery (removal of the main component of the tumor) was performed at a laser output of 20-40 watts. In the second stage of treatment, after 2-3 weeks, PDT was performed with remote laser irradiation of the entire vulvar surface with a light dose of 100-150 J / cm ² at a power density of 50-70 mW / cm ² and remote laser irradiation of the tumor location zone with a light dose of 200-300 J / cm ² at a power density of 150-200 mW / cm ² . However, an increase in the light dose to 200-300 J / cm leads to a number of negative consequences inherent in the prototype method.

Namely:

- the absence of a combined effect on the vulva and regional metastasis at 2a-3a stage of the disease;

- pronounced destructive tissue changes in the area of PDT and, as a result, prolonged wound healing against the background of significant pain reactions;

- rough scarring of tissues, up to stenosis of the vulvar ring, which does not meet the criteria for organ-preserving treatment;

- an increase in the duration of treatment of patients due to two-stage exposure;

- long-term rehabilitation of patients.

The invention is aimed at solving the problem of treating patients with an initial form of RV, as well as preventing the recurrence of the disease.

The use of the proposed method in clinical practice at the initial stage of the disease allows to achieve several therapeutic and economic results:

- ensuring an adequate antitumor effect;

- one-stage photo of dynamic impact;

- providing organ-preserving effect in women of reproductive age;

- a decrease in the total focal dose in the area of the tumor is almost two times compared with that specified in the prototype;

- the absence of destructive tissue changes in the area of PDT;

- reducing the time of epithelization of the wound surface;

- reducing the duration of rehabilitation of patients;

- expansion of indications for use in women of various ages.

These therapeutic and economic results in the implementation of the invention are achieved due to the fact that, as in the known method, the treatment of patients with RV is performed by PDT.

A feature of the claimed invention lies in the fact that PDT is performed by sequential intravenous administration of Radachlorin and per os administration of Alasens

The invention consists in the following.

Currently, the possibility of using organ-preserving treatment for stage 0 vulvar carcinoma (TisNOMO) and for art. The authors of the proposed method developed a PDT technique for patients with the initial form of RV without involvement of the clitoris in the tumor process. The inventive method involves the use of both the photosensitizer Radachlorin and endogenous fluorochrome Alesens.

The achievement of the above therapeutic results arises due to the low light and dark phototoxicity of Radachlorin in therapeutic doses, its good luminescence, solubility in the aquatic environment and the ability to be easily excreted from the body. In addition to the generation of singlet oxygen, radachlorin has a modifying effect on the plasma membranes of tumor cells when exposed to light with a wavelength of 662 nm. Subsequent exposure to light with a wavelength of 630 nm has a cytotoxic effect by inducing a type I and type II reaction. In a Type I reaction, Alasens, being in an excited state, directly reacts with biological structures. Type II reactions produce reactive oxygen species, such as superoxide and hydroxy radicals, which contribute a significant cytotoxic effect.

The method is as follows.

In the conditions of a semi-darkened room, the administration of Radachlorin in a dose of 1.0-1.2 mg / kg is carried out intravenously for 30 minutes. 1 hour after the end of the Radachlorin infusion, Alasens is administered per os at a dose of 30 mg / kg. 2 hours after receiving Alasens, fluorescence diagnostics is performed using spectrofluorimeters, followed by remote laser exposure through a quartz fiber using microlenses, to identify additional foci and to clarify the boundaries of the tumor site. On the same zone of the vulva carry out sequential light exposure by radiation with a wavelength of 662 nm (Radachlorin) and 630 nm (Alasens) at a dose of 80-150 J / cm ² . In this case, the regime of light exposure is chosen individually, taking into account the form and prevalence of the initial tumor process. In the zone of maximum fluorescence and spectral values, the energy density is 150 J / cm ² . In the treatment area after 2-4 days, necrosis begins to form, the rejection of which with subsequent epithelization of the wound defect occurs after 2-8 weeks.

The inventive method can be illustrated by the following examples.

Example 1

Patient B., 73. Clinical diagnosis: Cancer of the vulva Ia CT (T1aN0M0). In May 2008, the formation in the region of the lower third of the left labia minora to 1.5 cm in diameter was excised. Morphological study No. cons. 3118/08: intraepithelial squamous cell carcinoma, which occupies almost the entire surface of the pieces, to the burned edges, with microfoci, blurring of the basement membrane, which is suspicious for microfoci of invasion. A comprehensive examination of data for distant metastases was not obtained. Given the initial stage of the disease, the localization and prevalence of the tumor process, the age of the patient, a burdened somatic history and the high risk of performing surgical treatment in the amount of vulvectomy, fluorescence diagnostics and PDT of the vulva were performed on 18.06.08. In the conditions of a semi-darkened room, the administration of Radachlorin in a dose of 1.2 mg / kg was carried out intravenously for 30 minutes. 1 hour after the end of the Radachlorin infusion, Alasens was administered per os at a dose of 30 mg / kg. 2 hours after receiving Alasens in order to identify additional foci and clarify the boundaries of the spread of the tumor focus, fluorescence diagnostics was performed, followed by remote laser exposure through a quartz fiber using microlenses. The same vulvar area was sequentially exposed to radiation with a wavelength of 662 nm (Radachlorin) and 630 nm (Alasens). Irradiation doses: Radachlorin: output power - 1.2 W, energy power - 800 mW, energy density - 5 positions 80 J / cm ² , 1 position - 150 J / cm ² (in the zone of maximum fluorescence); Alasens (wavelength 630 nm): output power - 1.2 W, energy power - 600 mW, energy density - 6 positions 80 J / cm ² . In a spectrometric study of tissues after irradiation with Radachlorin and Alasens, significant changes in the indicators were noted, indicating the effectiveness of the treatment.

After a treatment session in the PDT zone, moderate exudation and swelling of the tissues, hemorrhagic necrosis were noted. During the control examination after 3 months. diagnosed with complete regression of foci of initial vulvar cancer with epithelization in the PDT zone without scarring.

Example 2

Patient B., 41. Clinical diagnosis: Primary multiple metachronic cancer:

1. Cr in situ of the cervix. Condition after surgical treatment (11.06 g.); 2. Cr in situ of the vulva. Condition after two sessions of PDT of the vulva. Morphological study No. P 5192-95 / B: micro-foci of severe dysplasia and cr in situ of the epithelial cover, coilocytosis, hyperkeratosis, acanthosis. A comprehensive examination of data for distant metastases was not obtained. Given the initial stage of the disease, the localization of the tumor process, the patient’s age and the possibility of conservative organ-preserving treatment in December 2008 and February 2009, two PDT sessions were performed with fluorescence diagnosis of the vulva. In conditions of a semi-darkened room, Radachlorin was administered iv in a dose of 1.0 mg / kg in a sequential manner for 30 minutes. 1 hour after the end of the Radachlorin infusion, Alasens was administered per os at a dose of 30 mg / kg. 2 hours after receiving Alasens in order to identify additional foci and clarify the boundaries of the spread of the tumor focus, fluorescence diagnostics was performed, followed by remote laser light exposure through a quartz fiber using microlenses. The same vulvar area was sequentially exposed to radiation with a wavelength of 662 nm (Radachlorin) and 630 nm (Alasens). Irradiation doses: Radachlorin: output power - 2.0 W, energy power - 800 mW, energy density - 5 positions 80 J / cm ² , 1 position - 150 J / cm ² (in the zone of maximum fluorescence); Alasens (wavelength 630 nm): output power - 1.2 W, energy power - 600 mW, energy density - 6 positions 80 J / cm ² . A spectrometric study of the tissues after irradiation with Radachlorin and Alasens noted significant changes in indicators indicating the effectiveness of treatment, which was morphologically confirmed over the next 6 months.

The inventive method has significant advantages and meets the criteria of patentability.

Claims (2)

1. The method of photodynamic therapy of patients with vulvar cancer, characterized in that photodynamic therapy is performed by sequential intravenous administration of radachlorin and per os administration of alasens and subsequent remote surface light exposure to laser radiation with a wavelength of 662 nm in a dose of energy density of 80-150 J / cm ² and with a wavelength of 630 nm in the same dose of energy density using a quartz fiber equipped with a microlens. 2. The method according to claim 1, characterized in that radachlorin is administered at a dose of 1.0-1.2 mg / kg, alasens is administered per os at a dose of 30 mg / kg.