Methods of treating patients with locally advanced uterine cancer

FIELD: medicine.

SUBSTANCE: there are performed beam therapy, intracavitary therapy and chemotherapy. For 5-7 days before the beginning of the radiation, Colagel-Beta with 1 β-interleukin 20 ml is introduced into a vaginal tube daily. Each session of the intracavitary therapy is preceded by introducing Colegel with 5-fluoruracil 20-25 ml into an uterine cavity and exposed for 30-40 minutes. Besides, from the beginning of the beam therapy 40-50 minutes after the radiation session, sodium alginate gel 20 ml containing methyluracil, dimethyl sulphoxide and hydrocortisone are introduced into a rectum and a bladder in a therapeutically effective amount. 5-10 procedures are performed.

EFFECT: providing faster regression of the tumour, reducing the rate and severity of radiation injuries of the rectus and bladder adjacent with the uterus with no risk of severe systemic toxic manifestations, including in senior patients with comorbid inoperable diseases and extended tumours.

3 ex

 

The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with locally advanced common forms of cervical cancer or cancer of the womb.

In the incidence of malignant neoplasms of the female population of Russia cancer of uterine body takes 3rd place (7.1%) and 1st place among malignant tumors of the female genitalia, in the structure of morbidity in women with malignant tumors in the world, cancer of the uterus occupies the 7th place.

Radiation therapy is used in 80% of patients with carcinoma of the cervix and uterine body as a combined treatment, as well as an independent method of treatment. But still 35-45% of patients, despite treatment, die from the underlying disease, and 10-35% of patients experiencing radiation damage to the pelvic organs, bladder and rectum.

One of the promising ways of increasing the effectiveness of radiation treatment is to strengthen the damaging effects of radiation to the tumor with radiomodification agents, and the use of radioprotectors to protect normal organs and tissues.

As radiomodification drugs currently widely used 5-fluorouracil, simultaneously with cytotoxic properties. However, to achieve radiativeconvective drug required intravenous administration of relatively high doses of this drug, what often limited by the development of toxic manifestations.

There is a method of treating patients with locally advanced common forms of cervical cancer, including chemotherapy 5-fluorouracil for 5 days daily with subsequent simultaneous introduction of the platinum source of drug and radiation therapy according to the scheme of dynamic fractionation of the dose. Additionally injected gel "Collegel" Derinat once a day in the vaginal tube and at the same time as the micro into the rectum in the first 5 days of treatment, then 3-4 hours before or 1-2 hours after each session and after a course of radiation within 2-3 weeks continue instillation in the vaginal tube in the same volume (Patent RF №2393897, IPC A61K 31/513, publ. 2010).

The disadvantage of this method is the possibility of developing toxic effects of 5-fluorouracil with its infusion introduction (decreased number of white blood cells and thrombocytopenia), in addition platinum drugs have an increased toxicity, poorly tolerated by people in the older age group, so it is not always possible to undertake a full course of chemotherapy.

There is a method of treating patients with locally advanced common forms of cervical cancer, including external irradiation and the use of chemotherapy, United with autoplasma (Patent P is No. 2261706, IPC A61K 31/282, publ. 2005).

The disadvantage of this method should be considered as the use of plasma, requiring the intake of large amounts of blood, strict antiseptic and sterilization procedures, i.e. how complex in execution, in addition, only external irradiation cannot be considered an adequate method of treatment of locally advanced cervical cancer.

There is a method of treatment of locally advanced cancer of the uterine body (Patent RF №2243771, IPC A61K 31/513, publ. 2005), including the use of chemical drugs and intrauterine irradiation. On the first day of treatment interstitielle peritumoral administered cyclophosphamide, the second day into the uterine cavity on creamy basis injected fluorouracil or adriablastin, the next day, spend the session intracavitary irradiation, the course may be repeated three times with a 6-day break.

The disadvantage of this method is inefficient, especially when a large tumor volume, high probability of toxic manifestations, because it does not enter one drug, and the number of different drugs, such as cyclophosphamide, adriablastin, 5-fluorouracil.

The closest is a method of treating patients with locally common forms of uterine cancer, including remote and potrebonosti radiation therapy, chemotherapy (I. Stolyarova. Radiotherapy of advanced endometrial cancer with or without metrondazole as radiosensitizcr. Zerbinis Medical Publications. Printed in Greece. Journal of BUON 5: 411-414, 2000.). Cancer of uterine body got mixed beam therapy by alternating intracavitary and remote exposure. Before each session intracavitary irradiation in the uterine cavity was entered metronidazole (MZ), dissolved in dimethyl sulfoxide (DMSO). To obtain this solution 1-2 g of crystalline MOH was dissolved in 10 ml DMSO. The prepared solution was injected into the uterine cavity ex tempore.

The disadvantage of this method is that in the treatment of locally advanced tumours of the uterus actually there is no substrate for the action of metronidazole with as radiosensibility donor-Accenture properties, resulting in exposure due to undergoing radical processes generating active radicals, causing regression of tumors, for this area it is impossible to achieve the desired effect, since, as a rule, these tumor tissue well oksigenirovannym due to the development of pathological neovascularization.

The invention aims to remedy these disadvantages, increasing the effectiveness of treatment by increasing the rate of tumor regression, stabilization of the tumor process, prevention of postradiation complications without the risk of severe toxic manifestations of systemic nature, including the elderly against the TA with additional systemic diseases, not to be surgical procedure, and with large tumors, more than 120 cm3volume.

To solve the tasks performed intracavitary and external beam irradiation, chemotherapy. This proposed within 5-7 days before the start of radiotherapy sessions to introduce in the vaginal tube "Collegel-Beta 1, beta interleukin in a volume of 20 ml daily. Immediately before each session intracavitary irradiation in the uterus it is necessary to enter 5-fluorouracil on the media with high viscosity, namely gel "Collegel" with 5-fluorouracil in a volume of 20 ml to 25 ml (depending on the volume of the uterine cavity defined by ultrasound) with exposure time of 30-40 minutes. 40-50 minutes after a session of remote radiation to enter into the rectum and the bladder 20 ml of gel on the basis of sodium alginate containing methyluracil, dimethylsulfoxide (DMSO) and hydrocortisone in therapeutically effective amounts. Since the beginning of the course remote irradiation carried out 5-10 of these procedures.

The implementation of the method is demonstrated on specific clinical examples:

Example 1

Patient S., 68, was in MCRT diagnosed with cancer of uterine body Art. III, hypertension Art. II, diabetes mellitus. In the clinical-laboratory examination revealed the distribution process at the parametrium, because h is th execution of surgical intervention was considered impossible. Tumor volume was 140 cm3. The only possible method of treatment was found chemoradiotherapy.

The patient was treated by the proposed method includes courses intracavitary and remote exposure. However before irradiation was carried out the application in the vaginal tube "Collegel-Beta 1, beta interleukin. The gel was injected daily with 20 ml within 7 days.

Immediately before each session intracavitary irradiation in the uterine cavity was injected 20 ml of "Collegel" with 5-fluorouracil, the duration of application was 40 minutes while she was on the gynecological chair.

The introduction of the drug into the uterus of the patient was transferred satisfactorily, side effects and complications associated with the drug, was not observed.

Subsequently the patient was transported to the canyon for holding intracavitary irradiation. The session was held at the AGAT-WU using metrostate 3-channel type. A single absorbed dose at point a was 5 Grams. Number of sessions - 10, with a frequency of 2 times per week. The total absorbed dose at point a was 50 Gy.

Then was appointed external beam radiation for LINAC-20 MeV to 4 Olney methods fields h see Single focal dose points was 2 Gy, and the total is 44 Grams. Were egene is but 10 sessions this exposure.

40 minutes after 1-5 sessions of remote exposure to the rectum and bladder were injected with 20 ml of gel on the basis of sodium alginate containing methyluracil, dimethylsulfoxide and hydrocortisone in a therapeutically effective amount, namely, in wt.%: methyluracil - 5, DMSO - 5 and hydrocortisone - 0,4.

As a result of therapy achieved initial clinical cure, which was recorded 7 days after the treatment. This indicates an increase in the rate of regression of the tumor of uterine body, which was confirmed by the data of cytomorphological studies of material from the uterine cavity, and ultrasound data. After 10 treatments intracavitary irradiation and 22 remote session therapy proposed course of treatment, tumor volume was significantly reduced by 50%, after treatment tumor volume was 75 see

It should be noted that similar results of treatment of patients with such amounts of destruction (140 cm3previously could not been reached.

During examination after 6 months found a stabilization process.

Example 2

Patient P., aged 63, was in MCRT diagnosed with cervical cancer III In Art., 2-sided parametric variant, exophytic form of growth. Histologically, squamous non-squamous cancer. Tumor volume by ultrasonography was 180 cm in volume of 20 ml daily.

Were treated by the proposed method.

Similar to that described in Example 1 was performed application in the vaginal tube "Collegel-Beta 1, beta interleukin within 5 days prior to exposure.

Given the exophytic tumor shapes, holding intracavitary irradiation in the first stage was impossible.

Due to the above reasons, the irradiation was started with remote radiation therapy using open fields size h see a Single absorbed dose metering points (points a and b) was 2 Gy. The total dose to the pelvis was brought to 30 Gr. Conducted 15 sessions of exposure daily. After 1-10 sessions remote exposure 40-50 minutes was introduced into the rectum and the bladder 20 ml of gel on the basis of sodium alginate containing methyluracil, DMSO and hydrocortisone in therapeutically effective amounts (analogously to example 1).

The tumor was reduced to 135 cm3. Then the irradiation was continued in the form of intracavitary gamma-therapy, which was held at the AGAT-WU 1 time per week, only 7 procedures. Single focal dose at point a was 7 Grams. The total dose at point a - 49 Gr.

Immediately before each session intracavitary irradiation was introduced into the uterine cavity (given the size of the uterine cavity defined by ultrasonography) 25 ml of the gel, the number of the gel with 5-fluorouracil with an exposure time of 40 minutes.

As a result of therapy was achieved stabilization process. According to cytomorphological studies, tumor cells were detected after treatment. According to the ultrasound, after this first course of therapy there was a significant decrease in the size of the cervix and body of uterus (V tumor - 85 cm3), i.e. it was noted the increase in the rate of regression but compared to treatment by standard techniques similar degree of neoplastic processes. It should be noted that when such amounts defeat a similar result is achieved no more than 5-10% of cases.

Example 3

Patient D., 72 years old, was hospitalized in MCRT diagnosed with cancer of uterine body Art. II Histologically - moderately differentiated adenocarcinoma of the endometrium. Tumor volume was 120 cm3. Given the presence of the patient severe comorbidity (hypertension III degree, the cerebral circulation from 01.2010,; diabetes mellitus type II, and expressed obesity) the method of choice was radiation therapy.

A complication of the underlying disease was the presence of pyometra. Treatment was started with the introduction in the vaginal tube "Collegel-Beta 1, beta interleukin but 25 ml daily for 5 days.

Before each session intracavitary irradiation in the uterus enter and 25 ml "Collegel" with 5-fluorouracil. The exposure time was 30 minutes, during which she was on the gynecological chair. The introduction of the drug into the uterus did not cause any complications. The session was held at the AGAT-WU. A single absorbed dose at point a was 5 Grams. Number of sessions - 10, with a frequency of 2 times per week. The total absorbed dose at point a was 50 Gy.

The second phase of radiation therapy was external beam radiation for LINAC-20 MeV, 3 times in Pedalo fields complex spatial configuration by summing the absorbed dose at points In - Gr 2;

the total absorbed dose at the point of account amounted 42-44 G, the number of procedures 5.

After each of the 5 sessions of remote exposure through 50 minutes into the bladder and rectum were injected with 20 ml of gel on the basis of sodium alginate containing methyluracil, DMSO and hydrocortisone. This allowed to undergo radiation treatment without any reactions and complications.

As a result of therapy was achieved initial clinical cure. This was confirmed by cytological and morphological studies of material from the uterine cavity, taken after the end of radiotherapy. V tumor was 65 cm3.

Conclusion:

Integrated chemo-and radiotherapy patients aged over 60 years with locally widespread the United cancers of the uterus allows you to reach after the first course of treatment for primary clinical cure with reduced tumor volume by 40-50%, even in large volumes.

When using the proposed method increases the speed of the radial regression of malignant tumors of the cervix and uterine body (double time reduction of tumor volume 8±1 days; control 12±1 day), increases the survival rate of the patients with extensive tumors of the cervix and uterine body (2-year survival rate is 79%, in control - 47%). The method allows for effective prevention of the complications of radiation from the side adjacent to the uterus organs, resulting in reduced frequency and severity of radiation injury of the rectum (3,5% against 13.6% in the control) and bladder (3,5% against 7.7% in the control group), which improves the quality of life of patients and increases the effectiveness of the treatment.

A method of treating patients with locally common forms of uterine cancer, including remote and intracavitary radiation therapy, chemotherapy, characterized in that it is injected into the vaginal tube within 5-7 days before radiation "Collegel-Beta 1, beta interleukin in a volume of 20 ml daily, immediately before each session intracavitary radiation therapy exercise introduction into the uterine cavity "Collegel" with 5-fluorouracil in a volume of 20 ml to 25 ml with an exposure time of 30-40 minutes and after sessions remote exposure 40-50 minutes is introduced into the rectum and the bladder 20 ml of gel-based Algin is the sodium, containing methyluracil, dimethylsulfoxide and hydrocortisone in therapeutically effective amounts, with the start of the course for distance irradiation carried out 5-10 of such procedures.



 

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2 ex, 1 tbl

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2 ex

FIELD: medicine.

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14 cl, 3 dwg

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2 dwg

FIELD: medicine.

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1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, pulmonology, radiology, radiation therapy of non-small-cell lung cancer. Sessions of the local radiation therapy are daily to a total focal dose equivalent to 60-70 Gy, in a dynamic dose fractionation mode at a single focal dose of 4-2 Gy. Additionally, three times a week immediately after the local radiotherapy session, an upper part of substernal notch to diaphragmare exposed to subtotal irradiation at a single dose of 0.1 Gy to a total dose of 1 Gy.

EFFECT: method provides reducing a risk of local recurrence, distant metastasis, and a severity of acute radiation reactions and injuries, eg pneumonitis, esophagitis, reducing the hematopoietic complications, complete tumour regression in 15,6% of patients with an average life expectancy of 18 months.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology and endocrinology, and can be used for treatment of endocrine ophthalmopathy. For this purpose introduced are: galium heel is introduced in dose 10 drops in 50-100 ml of water 3 times per day, for 3 weeks, reneel in dose 1 tablet sublingually 3 times per day for 3 weeks, injections of cerebrum compositum under skin in dose 2.2 ml 2 times per week, with 3-day interval, 5 injections in total, starting from the first day of treatment, injections of coenzyme compositum under skin in dose 2.2 ml 2 times per week, with 3-day interval, 5 injections in total, as well as hirudotherapy 2-3 leeches on temporal area, starting from the first day of treatment, two times per week, 4-6 procedures in total, with 3-day interval, radiotherapy, starting from the first day of treatment, by means of beta-applicators on projection of thickened muscles with radionuclide Ruthenium-106+ Rhodium 106, 5 sessions, 200 cGy each, daily.

EFFECT: method makes it possible to increase efficiency of treatment of endocrine ophthalmopathy due to reduction of edema of retrobulbar tissue and extraocular muscles with the lowest number of side effects and improvement of parameters of blood of thyroid gland hormones.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to traumatology and biotechnology, and may be used for the biocompatible polymeric structure formation in bone tissues. That is provided by a puncture approach to a filled cavity in the bone tissues. That is followed by filling the cavity with a polymeric gel compound containing 55-97.7 wt % of the biocompatible polymer polylactide of a particle size of 50 to 100 mcm, 0.3-45 wt % of magnetic nanoparticles of ferric oxide of a particle size of 10 to 100 nm, the gelling agent maltodexrin in the amount of 0.5 to 50 wt % of the weight of mixed polymer and magnetic nanoparticles, as well as distilled water in the amount of 0.5 to 100 wt % of the weight of a dry mixture of the polymer, magnetic nanoparticles and gelling agent. A solid three-dimension structure is formed. That is accompanied with heating the compound throughout by exposing to an alternating magnetic field at frequency 500 kHz and amplitude 500 E for 3-5 minutes. Where appropriate slow down the process of heating the compound, it is additionally exposed to a direct magnetic field at amplitude 1000 E applied either to the whole formed volume, or locally depending on the problem to be solved.

EFFECT: method enables forming the biocompatible three-dimension structure in the specified cavity of the bone tissue with minimum surgical intervention.

1 dwg

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