RU2238082C2 - Method of palliative treatment of extended prostate cancer with metastatic backbone damage - Google Patents

Abstract

FIELD: oncourology.

SUBSTANCE: method comprises intralumbal administration of hydrocortisone suspension in combination with synestrol. Suspension is introduced into intervertebral gap from Th12 to L5, whereas 2% oil solution of synestrol is introduced in amount 80 mg and 25% hydrocortisone suspension in amount 125 mg, fife times each other day.

EFFECT: enabled effective relief of chronic painful syndrome without system side effects and retarded appearance of pains in adjacent vertebrae.

1 tbl

Description

The invention relates to medicine, in particular to oncology, urology, and can be used in the treatment of patients with advanced prostate cancer with metastatic damage to the spine.

A known method of bilateral orchidectomy. In most countries, bilateral orchidectomy is still considered the treatment of choice for advanced prostate cancer. As a result of such surgery, the concentration of circulating testosterone is reduced by 95%, and often, already on the first day, after it a favorable effect can be obtained. After castration, acute degenerative changes occur, spreading to the glandular and muscle elements with the subsequent development of connective tissue in them. Although orchidectomy has a palliative effect in 70-80% of patients, the surgical intervention itself is not without drawbacks [Dunaevsky Y.A., Arie V.M., Myshko I.V. Indications for castration in prostate cancer. On Sat "Diagnosis and treatment of oncological diseases", 1991, p.134-138].

Orchidectomy is irreversible and its beneficial effect for those 20-30% of patients whose tumor is not hormone-dependent can be challenged. In addition, most patients with prostate cancer are elderly people, and therefore surgical intervention and general anesthesia sometimes pose a significant risk to their life. For younger patients, this is a severe psychological trauma. Side effects of castration are loss of sex drive and impotence, hot flashes and gynecomastia, osteoporosis, and psychological disorders.

A known method of hormonal therapy for generalized prostate cancer, including the use of estrogen (honvan, estradurin, synestrod, etc.). The results of estrogen therapy in the treatment of newly diagnosed patients with advanced prostate cancer are approximately the same in all countries: full regression - 2%, partial regression - 44%, one-year survival - 70-78%, five-year survival - 20-30%. When evaluating the effectiveness of treatment, there is no complete regression of the tumor. More often with hormone replacement therapy, a 2% sinestrol solution of 60-80 mg daily is administered intramuscularly for 2.5-3 months. Upon reaching the clinical effect after a course of treatment, patients are transferred to maintenance therapy. Sometimes a combination of estrogen therapy with the administration of 20–40 mg prednisone daily is effective [Sviridova T.V. Complex hormonal radiation treatment of stage IV prostate cancer patients. In the book: Plenum of the All-Russian. total Urologists, Saratov, 1994. - S. 170-171].

In the pathogenesis of cardiovascular complications during estrogen therapy, the leading place is occupied by disorders in the blood coagulation system (60-70%), there is an increase in blood platelet aggregation, a decrease in the concentration of antithrombin factor III and fibrinolytic activity (30-40%). The highest risk of severe cardiovascular complications in the first 6 months of treatment. High doses of estrogen inhibit liver enzymes, thereby contributing to the development of toxic hepatitis in 80% of cases, urodynamic disorders with significant dystrophic changes in the kidneys occur in 85% of patients. Estrogenic drugs have a damaging effect on the functional activity of the physiological system of immunity from 80 to 100% of observations.

A known method of interrupting the flow of afferent pain impulses, i.e. blockade of the sympathetic ganglia, in patients with severe irrepressible pain with metastatic damage to the spine in the form of a nerve block. Epidural and subarachnoid chemical denervation (alcohol, phenol, etc.) is based on turning off pain sensitivity by exposure to a neurolytic drug, leading to the destruction of sensitive nerve posterior roots [V.A. Koryachkin, V.I. Strashnov. Spinal and epidural anesthesia. - St. Petersburg: Publishing House LLC St. Petersburg Medical Publishing House, 2000, p.95].

A known method of intralumbar chemo-hormonal exposure in metastatic tumors of the nervous system. Glucocorticoid hormones are able to alter the expression of genes encoding the synthesis of DNA, RNA and proteins for transcription and translation apparatuses. Against the background of dehydration therapy, endolumbar administration of 125 mg of hydrocartisone and methotrexate is carried out at the rate of 2 mg / kg of body weight. The effectiveness of intralumbar administration of hydrocortisone is associated not only with direct anti-inflammatory and antitumor effects. Activation of diencephalic, hypothalamic-pituitary structures is associated with neuroendocrine (stimulation of gluconeogenesis) functions. The main place of application of the drug combination is metastatic tumor formation of the brain. [Komissarenko V.P., et al. Modern ideas about the mechanism of action of glucocorticoid hormones // Physiological Journal.-1982.- No. 6, - p. 721-723].

Disadvantages: not used in the treatment of metastatic prostate cancer.

The objective of the invention is to reduce pain in patients with prostate disease.

The problem is solved in that in a method of palliative treatment of generalized cancer, including intralumbar administration of a suspension of hydrocortisone, in combination with it, a 2% oil solution of sinestrol in the amount of 80 mg is administered five times five times a day. Hydrocortisone is administered as a 25% emulsion in an amount of 125 mg.

The method is as follows.

In the patient’s position on the side, with the knees brought to the stomach and the bent head located in the same horizontal plane with the body, the puncture is performed in one of the intervertebral spaces from Th12 to L5. The needle for spinal anesthesia is injected strictly along the midline between the spinous processes in accordance with the slope of the spinous processes. The depth that the needle enters ranges from 4.5 to 6.0 cm, an average of 5.5 cm. By the time of puncture of the dura mater, the needle cut plane is directed longitudinally to the fibers, the outflow of cerebrospinal fluid from the needle pavilion is an absolute sign of accurate localization. To facilitate puncture, it is most advisable to use 18-20 G needles with Grawford sharpening. Medicinal effect is carried out by a combination of a 2% oil solution of Sinestrol at a dose of 80 mg and a 25% suspension of hydrocortisone 125 mg. In order to create adequate analgesia, it is advisable to administer this combination of hormones five times into the spinal canal with an interval between administrations of one day. The course of treatment is carried out for 10 days with a total administration of sinestrol at a dose of 400 mg and hydrocortisone 625 mg. After the introduction of hormones, the patient is recommended to lie on his stomach without a pillow for 30-60 minutes to reduce the flow of cerebrospinal fluid into the epidural tissue through a puncture hole in the dura mater and reduce the likelihood of cephalgia.

According to the proposed methodology, 27 patients began treatment. Two of them were not included in the development, refusing to conduct hormone therapy after the first and third injections. In the main group, 3 patients were treated twice in the range of 9-14 months (table).

The main clinical manifestation of prostate cancer was pain in the bones with restriction and stiffness of movements, up to paraplegia and paresis. The average number of bone metastatic lesions in the group of patients at the time of treatment initiation was 9 ± 5.

Like any invasive treatment, endolumbar hormone therapy does not exclude the possibility of a number of complications. The following complications were observed in our patients for intrathecal drug treatment: hypotension - 4 (16%); headache (cephalgia with severe headache, especially in the occipital region, accompanied by dizziness, nausea, vomiting, stiff neck) - 1 (4%).

Severe complications occurring after spinal puncture (injury to the spinal cord or its roots, paresis of cranial nerves with neurological complications, aseptic meningitis, air embolism, horse tail syndrome, adhesive arachnoiditis), we did not note.

Additional prescription of anti-inflammatory and antimicrobial agents is not required.

Treatment control. Of the 25 patients, at the time of control (1998-2000), 16 lived, and 12 (75%) retained the analgesic effect obtained as a result of the treatment. The cause of mortality in all cases considered was the progression of the underlying disease.

Using the proposed endolumbar method of administering a combination of hormonal drugs has the following advantages:

- effectively relieves chronic bone pain syndrome in patients with metastatic spinal lesions for 8-14 months;

- delays the appearance of new foci of pain in adjacent vertebrae, avoiding systemic side effects of estrogens;

- can be used as an independent method of treatment or as an addition to radiation or drug therapy;

- better tolerated by patients than radiation therapy with its complications;

- reduces the costs associated with treatment and hospital stay.

Claims (1)

A method for palliative treatment of advanced prostate cancer with metastatic spinal injury, comprising intralumbar administration of a suspension of hydrocortisone in combination with synestrol, characterized in that the suspension is injected into the intervertebral space from Th12 to L5, wherein a 2% oil solution of sinestrol is administered in an amount of 80 mg, hydrocortisone in the form of a 25% suspension - in an amount of 125 mg, five times a day.