Method for treating relapses of uterine cervix cancer
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with treating patients with uterine cervix cancer with relapses in parametral fiber and in case of no possibility for radical operative interference and effect of previous radiation therapy. During the 1st d of therapy one should intravenously inject 30 mg platidiam incubated for 1 h at 37 C with 150 ml autoblood, during the next 3 d comes external irradiation per 2.6 G-r. During the 5th d of therapy one should introduce the following composition into presacral space: 60 ml 0.5%-novocaine solution, 1 ml hydrocortisone suspension, 2 ml 50%-analgin solution, 1 ml 0.01%-vitamin B12 solution, 1.6 g gentamycine, 800 mg cyclophosphan, 10 mg metothrexate. These curative impacts should be repeated at mentioned sequence four times. The method enables to decrease radiation loading and toxic manifestations of anti-tumor therapy at achieving increased percent of tumor regression.
EFFECT: higher efficiency of therapy.
The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with cervical cancer with recurrence in the parametrial tissue and the absence of radical surgery and the effect of previous radiation therapy.
Know the treatment of recurrent cervical cancer with the use of ionizing radiation with prior anticancer chemotherapy or without the last (Evelopmen Guide "gynecology". L., "Medicine", 1989).
As indicated by the author, radiation therapy in full in the absence of a significant effect in many cases, leads to complications such as vaginal and premonicion-vaginal fistula. Patients are exposed to unnecessary harmful effects of radiation.
Chemotherapy for cervical cancer during its recurrence is not widespread due to the resistance of tumors to cytotoxic drugs and their high toxicity, which is very important for this cohort of patients.
It should be noted that the prognosis of patients with recurrent cervical cancer is very bad, one year after their manifestations live only 10-15% of patients. When the parametric recurrent cervical cancer surgery in radical extent technically feasible and not biologically justified. When choosing a method of radiation those who FIPA most important are features of primary treatment. In cases of ineffective radiation treatment, carried out early in full, develops a pronounced resistance of the tumor.
Only the use of relatively large total absorbed doses delivered to the recurrent node in parametric, may cause long-term cure, and it is usually not possible due to the fact that the dose tolerant load of healthy tissues, including related bodies, almost exhausted.
There is a method of treatment of parametrial recurrence of cervical cancer (Efimov A.G. "Medical rehabilitation of elderly patients with cervical cancer after combined radiation therapy abstract. Diss....Kida. the honey. Sciences., Rostov-on-don, 2001), including intravenous platydema at a dose of 120 mg/m2in the form of a one-hour infusion and intramuscular prospidina at a dose of 200 mg a day to a total dose of 2 g Platinum was dissolved in saline and injected in the background of overhydration, i.e. after transfusion of two liters of saline solution for one hour, after which he entered one liter of saline solution with 30 mg car stereo for 30 minutes To improve the tolerability of treatment for 30 minutes before infusion of platydema was administered 30 mg of prednisolone and 2 ml Relanium; two hours after the introduction of platydema intramuscularly injected 10 mg of cerucal, 2 ml droperidol the a and 2 ml Relanium. The interval between courses was 4 weeks. The number of courses identified in the course of treatment taking into account the effect of the treatment and condition of patients.
However, the effectiveness of the scheme in recurrent cervical cancer according to the author does not exceed 40%, and a percentage of the full regression is 12.5%. The stabilization of the recurrent lesion was noted in 19% of patients, and progression of the process on the background of treatment in 44% of patients. The second significant drawback schemes of chemotherapy, including platinum drugs is high toxicity. Complications typical of used doses of cytostatics, was observed in 70% of patients. Therapy of these complications are time-consuming and costly.
The aim of the present invention is to improve the immediate and remote results of treatment of patients with recurrent cervical cancer in the parametrium.
This goal was achieved by the fact that on the first day of treatment from the cubital vein taken 150 ml of blood into a sterile standard vial containing anticoagulant, gleyzer. In the same bottle add 30 mg of platydema and incubated 1 hour at 37° followed by reinfusing vial intravenous drip. In the second, third, and fourth days of treatment, patients received daily remote gamma-therapy is recommended for pelvic vyazovoi dose of 2.6 G ( three days - 7,8 G). On the fifth day of treatment, patients in the space enter: 60 ml of 0.5% solution of novocaine; 1 ml suspension of hydrocortisone; 2 ml of 50% solution of dipyrone; 1 ml of 0.01% solution of vitamin b12; 1.6 g of gentamicin; 800 mg of cyclophosphamide; 10 mg of methotrexate. Therapeutic effects is carried out in the specified sequence 4 times.
Analysis of the known methods of treatment of recurrent cervical cancer and developed enables us to conclude that the proposed method has novelty. The novelty of the method is to stimulate the body's immune system and radiosensibility input complex drugs.
In the available sources of information Russia, CIS and abroad guidance on this method of improving the immediate results of treatment parametrial recurrence of cervical cancer is not detected.
The invention is industrially applicable, as may be repeatedly reproduced and multiplied in health care, in hospitals and specialized therapeutic profile.
The method is as follows.
After conducting bimanual and ultrasound examination of the pelvic organs to patients with a diagnosis of recurrent cancer of the cervix is the introduction of anticancer chemotherapy. From a peripheral vein carries out the I fence 150 ml of patient blood into the vial with 50 ml of pulizia, add 30 mg of cisplatin, the resulting mixture was incubated at 37°C for 1 hour. Then on the background of standard overhydration produce reinfusion mixture. In the second, third, and fourth days of treatment is remote gamma-therapy is recommended for pelvic dose of 2.6 Grams. On the fifth day is an introduction to the space 60 ml of 0.5% solution of novocaine, 1 ml suspension of hydrocortisone, 2 ml of 50% solution of proteins, 1 ml of 0.01% solution of vitamin b12, 1.6 g of gentamicin, 800 mg of cyclophosphamide and 10 mg of methotrexate. All of these therapeutic effects are performed in the listed sequence four times.
For proof, here is the excerpt from the history of the disease, confirming the clinical effect of the treatment approach. An example of clinical application.
1. Patient S., born in 1944 (East. disease No. 6571/l), is under the supervision of RNII with 19.05.98. Diagnosis: cervical cancer T3NxMo, mixed growth form, vaginally-parametric option. Histogenesis No. 12977 from 19.05.98 - squamous cell carcinoma with keratinization.
In the period from 21.05.98 to 15.07.98 received combined radiation treatment. Remote gamma-therapy is recommended in the pelvic area conducted in static mode single focal dose of 2 Gy to a total dose at point a - 20 Gr, at point b - 42 Gr. Intracavitary With60therapy osushestvlyaetsya AGATE IN a single dose of 5 Gy at the rhythm of exposure 3 times per week to a total dose at point a 50 G and the point 16.7 Gr. The treatment is finished with a primary clinical recovery. In the process of treating early radiation reactions were not available.
After 10 months of dynamic observation, with a turnout of 12.05.99 for inspection, complaints nagging abdominal pain with irradiation to the left lower extremity, pain in the lumbar region. These complaints concerned about the patient in the last month. Mild signs of intoxication syndrome in the form of a subfebrile temperature in the evenings to 37,3°With, loss of appetite, weakness.
Local status. The vagina adhesive process, the fabric of normal color, clean. Line adhesion of the walls of the vagina without seals. The cervix thick, without pathological seals are fixed to the left arch. The uterus is normal size, dense, painless, limited in mobility. The degree of mobility of the pelvic floor is 0.5 see the Appendages are not defined. In the parametric space to the right scar tictacti. To the left is defined by dense infiltration of fiber, performing the parametric space from the edges of the uterus to the walls of the pelvis, pain during examination. Produced by needle biopsy of this area.
Cytological examination punctate parametrial space left No. 27255-56 from 12.05.99 - erythrocytes, among polymorphic cells of inflammation detected single cells plaskolite the CSOs cancer.
Ultrasound of the pelvic organs from 13.05..99 amount cervical 29.5 cm3the uterus and appendages correspond to normative values. The left internal iliac artery lazerette enlarged lymph node up to 2.5 cm in diameter.
With color and power Doppler mapping to the left of the cervix lazerette plot to the walls of the pelvis with multiple vascular components of irregular shape conglomerate type, characterized by the presence of vessels tortuous shape with arterio-arterial, arteriovenous anastomoses. When abnormal Doppler waveforms pathological vascular loci registered diskresident arterial blood flow with average index values of resistance - 0,51.
When KG image (14.05.99) to the left, in the projection parameters determined focal changes are unevenly chaotic nature in diameter from 0.3 to 0.9, see Diffuse component of infiltration, not beyond the fat density (45 EDN.), in contact with the muscular wall of the pelvis.
General analysis of blood from 12.05.99. HB - 98 g/L. er - 3,9×1012/l CPU - 0,9; lake. - 6,0×109/l as. - 2%, and fell. - 6%, segm. - 58%, limp - 26% (abs limp 1,56×109/l), MES - 8% (abs. mon 0,48×109/l ), ESR - 24 mm/hour.
The standard examination, which included fluorogram of the chest, ultrasound of the liver, kidneys - signs gave the frame metastasis have been identified.
The clinical diagnosis of cervical Cancer TNxMo, CL gr. II. Condition after combined radiation therapy. Recurrence of cervical cancer in the left parametrium.
Treatment is started. Autohemotherapy was held once a week: 17.05.99; 24.05.99; 31.05.99 and 07.06.99. Intravenously with normal hydration put on 30 mg cisplatin, incubated at 37°C for 1 hour with 150 ml of autologous blood of the patient
The introduction of 800 mg of cyclophosphamide and 10 mg of methotrexate in the composition is 0.5% solution of novocaine - 60 ml, gentamicin 1.6 g, suspension hydrocortisone acetate 2.5 percent to 1.0; ciankobalamin (Vit B12) of 0.01% to 1.0 ml, analgin 50% to 2.0 ml of 1 time per week: 21.05.99; 28.05.99 web; 04.06.99 and 11.05.99.
Other days, namely (18-20.05.99; 25-27.05.99; 01. - 03.06.99 and 08-10.06.99) was carried out remote gamma-therapy is recommended in mode 2 axial sector rotation (fields 7×16 cm, the distance between the axes of rotation 6 cm, RIO 75 cm, the swing angle 180°). Single focal dose of 2.6 Gy was delivered in 2, 3 and 4 days of the week, i.e. on the next day after a course of autohemotherapy and to the introduction of a mixture of drugs within four weeks of anti-chemoradiation treatment. Total for the entire cycle of treatment received drugs: 120 mg cisplatin, 3200 mg of cyclophosphamide, 40 mg of methotrexate. Total focal dose for both parameters amounted to 31.2 G that is relevant to the duty to regulate biological effect of 34 Gy in standard fractionation of a single dose of 2 Gy.
General toxic symptoms during treatment were absent. General analysis of blood from 14.06.99. HB - 96 g/l, er - 4,0×1012l CPU - 0,82; lake. - 4,4×109/l as. - 1%, and fell. - 13%, segm. - 55%, limp - 26% (abs limp 1.14×109/l), MES - 5% (abs. mon 0,22×109/l ), ESR - 14 mm/hour.
Blood biochemical parameters:
|urea||5.3 mmol/l||7.2 mmol/l||6.1 mmol/l|
|creatinine||for 95.3 mmol/l||113,1 µmol/l||102,1 µmol/l|
|total protein||63 g/l||67 g/l||63 g/l|
|total||5.7 µmol/l||8.5 µmol/l||8.5 µmol/l|
|free||not defined||not defined||not defined|
|associated||5.7 µmol/l||8.5 µmol/l||8.5 µmol/l|
|ALT-alaninemia-trasferase||0.4 mmol/l||0.2 mmol/l||0.2 mmol/l|
Local status at discharge. The vagina adhesive process, the fabric of normal color, clean. Line adhesion of the walls of the vagina without seals. Examination through the rectum. The cervix thick, without pathological seals. The uterus is normal size, dense, painless. The degree of mobility of the pelvic floor is 1.4, see the Appendages are not defined. In the parametric spaces of the right and left scar tictacti. Signs of infiltration of fiber no. The study painless.
Discharged from the hospital with clinical recovery. With a turnout of over 1 month after treatment, no complaints. Surveyed.
Ultrasound of the pelvic organs from 12.07.99 (one month after completion of treatment), the amount of the cervix 27.5 cm3the uterus and appendages correspond to normative values. Symptoms of retroperitoneal lymph nodes are not detected.
With color and power Doppler mapping positive dynamics. Determined hypovascular type of flow, kept single color loci and arteriovenous shunts. Architectonics vessels intact, without structural changes. For the spectral estimation of blood flow index of resistance - 0,82. In CT image (14.07.99) parametrial the aqueous space of the same type are defined gradevalue ocharovatelnye patterns in vascular variant structure.
With the clinical diagnosis of cervical Cancer Tangmo, CL gr. III. Condition after combined radiation therapy in 1998. Chemoradiation treatment parametrial recurrence of cervical cancer in 1999. Observed until January 2003, i.e. within 42 months, with no signs of recurrence and metastasis.
The proposed method was carried out treatment of 45 patients with recurrent cervical cancer in the parametrium. Before treatment and after its completion, all patients were examined in the mirrors, rectovaginal examination, General and biochemical blood tests, chest x-ray and excretory urography, radioisotope study of the kidney, ultrasound and computer hologramme of the pelvic organs, the condition of the lymphatic system, pelvis and paraaortal departments, needle biopsy with cytologic examination.
The effectiveness of the proposed method of treatment was 70%of them in 56% of cases had complete regression and 14% partial regression of recurrent tumor. The stabilization process is registered in 30%. The progression of the process is not detected in any case. The survival rate of 16 patients was 40-45 months.
The improved outcomes we see it as a combination of various positive factors, which consists in increasing the local concentration of x is Biopreparat, on the background objectively reduced the levels of total toxic their actions, sensitizing action of small doses of platydema against ionizing radiation and activation under the action of small doses of methotrexate cells of immune system of the body. An additional positive effect is due to the cessation of impulses along sensory nerve fibers under the action of novocaine, which, without significantly changing the resting potential of nerve fibers inhibits the processes of generation and propagation of action potential, which causes a kind of stabilization of membranes associated with the ability of local anesthetics to penetrate into the lipid layer of cell membranes. Stabilization of cell membranes, in turn, leads to local deposition of drugs in the area of recurrent growth. This happens on the background of anti-inflammatory therapy and anesthetic effect, which is also very important for this group of patients.
Technical and economic efficiency “treatment of recurrent cervical cancer” is that:
- increases the duration and improving the quality of life of patients;
- reduced radiation exposure and toxic side effects of anticancer therapy;
the result is a large percentage of regression of the tumor.
JV is a method for treatment of recurrent cervical cancer including the use of chemotherapy, United with Autocraft, and external irradiation, characterized in that on the first day of treatment intravenous 30 mg platydema, inkubirovanija 1 h at 37°With 150 ml of autologous blood, in the next three days conducting external irradiation with 2.6 G, in the fifth day in the space of introducing a mixture of 60 ml of 0.5%solution of novocaine, 1 ml suspension of hydrocortisone, 2 ml of a 50%aqueous solution of proteins, 1 ml of 0.01%aqueous solution of vitamin b12, 1.6 g of gentamicin, 800 mg of cyclophosphamide, 10 mg of methotrexate therapeutic effects repeat in sequence four times.
FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacology, pharmacy.
SUBSTANCE: invention relates to a medicinal agent used for prophylaxis and treatment of diseases and disorders associated with dysfunction of benzodiazepine receptors. This medicinal agent comprises compound of the formula (I)
. Compound of the formula (I) elicits high cardioprotective, neurotrophic, renoprotective activity and enhanced bioavailability.
EFFECT: valuable medicinal properties of compounds.
5 cl, 1 tbl, 1 ex
SUBSTANCE: method involves intravenously administering 0.1-1% aqueous solution of khlorin, selected from group containing photolon, radachlorine or photoditazine at a dose of 0.2-0.5 mg/kg or 0.2-1% aqueous solution of porphyrin like photogem at a dose of 0.2-1 mg/kg. Laser irradiation of blood is carried out 5-15 min later after beginning photosensitizer injection into cubital vein of one arm via laser light guide set in advance in the cubital vein of the other arm during 10-40 min at wavelength of 661-666 nm and power of 20-50 mW one session per day during 3-10 days with the aqueous solution of khlorin used as the photosensitizer, or laser irradiation of blood with wavelength equal to 630-633 nm during 10-45 min with power of 20-50 mW one session per day with the aqueous solution of porphyrin used as the photosensitizer. Repeated intravenous administration of photosensitizer is carried out 1-3 months later combined with repeated laser irradiation of blood.
EFFECT: reduced risk of tumor cells dissemination and metastasis development.
where R denotes phenyl, isopropyl or tert.butyl; R1denotes-C(O)RZin which RZmeans (CH3)3CO-, (CH3)3CLO2-, CH3(CH2)3Oh, cyclobutyl, cyclohexyloxy or 2-furyl and R2denotes CH3C(O)O-, and also to pharmaceutical compositions based on them and their use as protophobic agents to treat diseases of humans and animals
or their pharmaceutically acceptable salts, where Y and Z each for each case independently represents a D - or L-natural or unnatural-amino acid; n in each case independently is 0 or 4, (I) provided that both n cannot simultaneously be 0; and 0 or 4 (II)
moreover, these amino acids (I) are chain: X1-X2-X3-X4where X1represents Tyr or Trp, which may be protected by a BOC group; X2represents D-Trp; X3represents Lys, which may be protected by a BOC group; X4is a Nal, Tyr or Thr; m is 0; a represents N or R1b means HE or OR1; (II) X1is a natural or non-natural D - or L-isomer of Phe, Trp or Tyr, where in the case when X1is Tyr, an aromatic ring in its side chain optionally substituted by R6; X2is a D - or L-isomer of Trp; X3represents Lys; X4represents Opticheskie ring, disposed in its side chain may be optionally substituted by R6or in the case when X4is either Ser or Thr, the oxygen atom located in its side chain, optionally may be substituted by one or more R1