RU2241452C1 - Method for treating osseous metastasis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: the present innovation deals with chemoradial treatment of osseous metastases. The method includes distance gamma-therapy and medicinal therapy. Moreover, as medicinal therapy one should intravenously inject about 60-80 mg adriablastin, then 7-8 d later one should intravenously inject 5-fluouracil for 3-4 d at total dosage being 3-4 g. After a 3-d-long interval simultaneously with the onset of gamma-therapy one should intravenously inject a platinum-containing preparation at standard dosing for 5 d. Moreover, one should conduct irradiation during the first 3 d at a single dosage being 4 g, and the next ones per 2 g up to total dosage of 30 g. Repeated course should be carried out in 4-5 wk. The method enables to prolong and accelerate positive curative effect in the form of decreased painful feelings and pareses and, also, achieve complete destruction of metastases.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, namely to chemoradiotherapy of bone metastases of predominantly local osteolytic nature.

There is a method of drug treatment of bone metastases of bonephosomes according to the developed scheme, which with prolonged use can dramatically inhibit the growth of metastasis, which makes it possible to stabilize the patient’s condition for a while or even increase the comfort of his life (Bisphosphanates and metastsftic breast cancer. Lipton A., Cancer 2003, Feb 1; 97: 848 - 53).

The disadvantage of this method is that taking Bonefos only leads to temporary stabilization of the size of the metastasis, but cannot cause complete or partial destruction of the metastatic focus.

A known method of treating bone metastases, involving irradiation of a metastatic lesion according to the scheme: a single focal dose (ROD) of 4-5 Gy to a total dose of 20-25 Gy for 4-5 days (V.I. Chisov “Combined and complex treatment of patients with malignant tumors ”, Moscow,“ Medicine ”, 1989, p. 224 - 225).

The main disadvantage of this method is that in the process of its implementation only palliative tasks are solved, for example, temporarily rid the patient of a strong pain syndrome. In addition, in almost 50% of patients, the clinical effect cannot be achieved with this method.

Closest to the proposed is a method of treating bone osteolytic metastases, including locally distributed, including remote gamma therapy with an intensively concentrated course up to a total dose of 20-25 Gy, drug therapy of Bonefos in a daily dose of 11-16 g (RF Patent No. 2144398, publ. 2000).

The disadvantage of this method is that it can only temporarily weaken the adverse effects of metastasis in the bone and adjacent tissues, the impossibility of total lethal damage to the pool of tumor cells forming a metastatic focus, which inevitably entails the resumption of proliferation of tumor cells in metastasis further hematogenous distribution.

The task set by the authors is to eliminate these shortcomings by using the combined use of chemotherapeutic drugs and a course of radiation therapy according to the developed scheme, which allows increasing the cytotoxic effect of radiation on the metastatic lesion in the bone tissue by increasing the radiosensitizing effect. The proposed method allows to achieve complete destruction of bone metastasis, which leads to a prolonged disappearance of symptoms associated with the growth of metastasis in various parts of the skeleton.

For this, in the treatment of bone metastases, including remote gamma-therapy and drug therapy, it is proposed that 60-80 mg of adriablastin be administered intravenously for 1 day as a drug therapy, then 5-fluorouracil is administered intravenously for 7-8 days for 3-4 days in a total dose of 3-4 g, and after a 3-day break at the same time as the start of gamma-therapy, administer platinum-containing preparations in a standard dosage for 5 days, while irradiation in the first three days is carried out with a single dose of 4 Gy, and the following - 2 Gy to the sums arnoy dose of 30 Gy. Repeat the course after 4-5 weeks.

The use of adriablastin 7-8 days before the start of the infusion of 5-fluorouracil known for its radiomodifying properties potentiates the mechanism of the radiomodifying action of the latter, which creates favorable conditions for the fuller use of the cytotoxic effect of irradiation, carried out according to a scheme adapted for radiotherapy of bone metastases to radical doses against the background of parenteral use of a platinum-containing sensitizer for tumor cell death.

The method is as follows.

Destructive changes in bone tissue should be visualized radiologically. In the course of preradiation preparation, marking pictures are performed in two projections. The sizes of the fields are the sum of the sizes of the bone tumor focus plus 2 cm.

Be sure to consider tumor soft tissue infiltration, which is usually assessed by MRI. At the same time, a general analysis of blood and urine, blood biochemistry, ECG, radiography of the lungs, ultrasound of the liver, kidneys, lymph nodes of the abdominal cavity, axillary regions (if the tumor is localized in the bones of the upper limb) are performed. Treatment consists of two identical steps. On the 1st day of each stage, intravenous administration of adriablastin (pharmarubicin) is carried out in a dose of 60-80 mg. Then, after 7-8 days, 5-fluorouracil in a total dose of 3-4 Gy is administered intravenously for 3-4 days. After a 3-day break, simultaneously with the start of gamma therapy, cisplatin (platidiam) 20-30 mg is administered intravenously for 5 days for 5 days. Irradiation is carried out according to the following scheme: the first three fractions of 4 Gy, then 2 Gy to 30 Gy.

Bone metastasis tumor cells are chemoresistant. As a result of irradiation only, there is only a slight temporary decrease in bone metastasis. Using the proposed method allows to create optimal conditions in a tumor cell for enhancing radiosensitizing properties, since clinical observations have revealed that adriablastin has radiosensitizing properties like 5-fluorouracil and platinum-containing drugs, which leads to a high percentage of fatal injuries of tumor cells that form metastasis.

Example 1

Patient J., 52 years old, was referred for a consultation with a radiologist with a diagnosis of breast cancer metastasis in the bone of the thoracic spine at the level of TH 4-6, accompanied by lower paraparesis. In the process of performing x-ray of the spine and MRI, an osteolytic metastasis was revealed that destroys the bodies of TH 4-6 with compression of the spinal cord at the level of TH5. After examination in the radiological department, the patient underwent two stages of treatment according to the above scheme: adriablastin was administered iv 60 mg, after 7 days 5-fluorouracil was administered for 3 days, 1 g, after 3 days radiation was started, combined with the introduction of platidiam 30 mg iv for 5 days, while irradiation was carried out up to 30 Gy at each stage according to the proposed method. As a result, complete regression of lower paraparesis was noted. During the control MRI of the thoracic spine one year after treatment, destructive changes of the previous sizes remain in the area of ТН4-6, however, it was not possible to visualize the soft tissue component of metastasis. With a regular examination for 1.5 years, there were no signs of metastasis to other bone formations or visceral organs.

Example 2

Patient B. 60 years old, with scintigraphy of skeleton bones and radiography revealed two destructive lesions in the area of the right iliac bone, located at a distance of 4 cm. The patient received treatment according to the above scheme: adriablastin 80 mg, 5-fluorouracil 1 g for 4 days, the irradiation was carried out according to the scheme described in example 1. The pain syndrome disappeared after the completion of the 1st stage of treatment, as a result of which the patient stopped using the services of outsiders when moving. The second course was carried out after 5 weeks. When the control scintigraphy of the skeleton bones carried out after 6 months. after treatment, a decrease in the accumulation of radiopharmaceuticals in the area of metastases was noted. 12 months after treatment, the patient was examined in the radiological department - there were no signs of progression of metastases in the pelvic bones.

It should be noted the duration of the positive effect in the treatment of the proposed method, the absence of pain in the metastasis zone in patients, the disappearance of paresis.

The proposed method of treatment has been used by us for 4 years, it is well tolerated by patients, leading to the rapid disappearance of pain associated with metastasis. In the presence of spinal cord compression, paresis is significantly reduced at the end of the first stage of treatment. Only irradiation of bone metastasis led to a decrease in pain by a maximum of 6 months. The proposed method makes it possible to relieve the patient of pain for a period of at least three times as much. In addition, in most cases, complete destruction of the metastasis occurred, which, unlike the previously used palliative techniques, allows us to characterize the proposed method as a method of radical treatment of bone metastases.

Claims (1)

A method for treating bone metastases, including remote gamma therapy, drug therapy, characterized in that 60-80 mg of adriablistin is administered intravenously as a drug therapy, then 5-fluorouracil is administered intravenously over 7-8 days for 3-4 days a total dose of 3-4 g, and after a 3-day break, simultaneously with the start of gamma therapy, a platinum-containing drug is administered intravenously in a standard dosage for 5 days, while irradiation in the first three days is carried out with a single dose of 4 Gy, and the subsequent dose of 2 Gr to the sum a dose of 30 Gy, a repeated course is carried out after 4-5 weeks.