RU2090203C1 - Method for treating locally disseminated cancer - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves applying combined treatment completed with measures for preventing and correcting injuries in the immune system by bringing to norm the general number of leukocytes and the number of lymphocytes in leukocyte formula as well as other parameters of general blood examination. Biostimulation agent is administered to patients beginning from minimum therapeutic dose 2-3 days before starting treatment and all over the whole course of any antitumor treatment daily before taking meals between 7 and 9 o'clock. Each 2-3 days the dose is lowered for 30% when compared to the previous one. The second daily dose of the same biostimulation agent is to be added 5-8 days later after beginning the treatment course. The dose is to be given 2-2.5 h later after the first dose in the amount being 1.5-3 times as large as the first one. EFFECT: excluded immune depression and leukopenia. 2 tbl

Description

 The invention relates to medicine, more specifically to oncology, based on the development of the discovery of the USSR, diploma N 158 of 05.23.75, and can be used in combined treatment (chemoradiotherapy and surgical) of locally advanced cancer of the head and neck organs and other localizations.

 Currently, it is known that the tumor process develops against the backdrop of a defective immune system (Balitsky K.P. Vinnitsky V.B. Vorontsova A.P. Mechanisms of antitumor resistance. Kiev: Naukova Dumka, 1978, 268 pp. Bylinsky B.T. Volodko N.A. Shparyk Y. V. Immunological mechanisms of natural antitumor resistance. Kiev: Naukova Dumka, 1991, 246 pp.), Which is especially true for T-cell immunity, and the predominant non-specific adaptive reaction against which tumor growth occurs is stress. In other words, there is a decrease in nonspecific and antitumor resistance of the body. In this regard, the state of the body's protective systems, immune status, necessary for the effectiveness of the treatment of cancer, require correction.

 There is a method of increasing nonspecific resistance of the organism, based on knowledge of the laws governing the development of antistress adaptation reactions (ed. Certificate N 1474925, class A 61 K 35/78, 1984), which consists of taking biostimulants twice during the day: the first dose is 40-80 times less than the therapeutic dose, and the second, after an interval of 2-2.5 hours, 5-10 times more than the first dose.

 However, this method of increasing nonspecific resistance was developed not for cancer patients for the purpose of treatment, but to increase physical and mental performance and cannot be applied to cancer patients without the special development of another method.

 A known method of treating cancer of the head and neck (see Pachez A.I. Tumors of the head and neck. M. 1971; Pachez A.I. The current state and problems of treating patients with head and neck tumors. M.1983), including the use of advanced operations, radiation, chemotherapy.

 However, this method of treatment has drawbacks, namely, it leads to a deepening of disorders in the immune system and a further drop in nonspecific and antitumor resistance of the body. This is associated with the development of postoperative complications, severe intoxication, leukopenia or leukocytosis, lymphopenia, anemia, monocytosis and other disorders. These complications lengthen the treatment time, increase the consumption of medications, make it impossible to conduct a full course of chemo or radiation treatment, or with continuous courses lead to the development and deepening of stress and immunosuppression, which worsens the immediate results, indicators of the general status and emotional state of patients.

 The aim of the invention is the prevention and correction of disorders in the immune system without the use of special immunomodulators, using a specific regimen of biostimulator, normalize the number of leukocytes, lymphocytes and other parameters of the general blood test, reduce intoxication and postoperative complications, as well as reduce the side effects of chemo and radiation therapy .

 The goal is achieved by the fact that 2-3 days before the start of treatment and throughout the course of any special antitumor treatment, patients receive a daily biostimulant, starting from the lower therapeutic dose, and every 2-3 times, on an empty stomach, between 7 and 9 in the morning days, reduce this dose by 30% from the previous one, then 5-8 days after the start of taking the biostimulator, add the second dose of the same biostimulator every day 2-2.5 hours after the first dose 1.5-3 times the first dose and repeat the whole course repeatedly after reaching the magnitude of the first dose is 1/5 of the lower therapeutic in men and 1/7 in women.

 The selected parameters of doses and time of exposure are based both on theoretical studies of the patterns of development of antistress adaptation reactions that increase nonspecific, including antitumor, body resistance, as well as on experimental data, as well as on clinical studies. Changes in dose or time parameters compared to those indicated reduced the effectiveness of the method.

 The invention is new, because on the basis of the development of the discovery, immunosuppression is corrected, the number of leukocytes, lymphocytes and other parameters of the blood test is normalized, the number of complications and intoxications is reduced by taking the biostimulator daily, on an empty stomach, between 7 and 9 o’clock in the morning, when the weakest, most informative exposure, starting with the lower therapeutic dose and decreasing it every 2-3 days by 30% from the previous one, and then after 5-8 days adding a second dose at a certain time interval (2-2.5 hours) to e, higher than the first 1.5-3 times. Upon reaching the value of the first dose, 1/5 of the lower therapeutic in men and 1/7 of the lower therapeutic in women, the course is repeated many times. Impacts are made before and after surgery and during chemo-radiation treatment throughout the patient’s stay in the hospital.

 The invention has an inventive step, since for a specialist oncologist it does not explicitly follow from the level of medicine in this field of oncology, limited by the use of chemoradiation and surgical treatment methods, without the use of a special correction regime for immune system disorders without immunomodulators and without correction of the general status of the body.

 The level of medicine includes information that has become generally available in the world medical scientific literature and patent information regarding increasing the body's resistance, physical and mental performance of non-cancer patients without immunomodulators, is not known in the medical literature.

 The invention is industrially applicable, as it can be widely used in healthcare in the treatment of locally advanced cancer of the head and neck organs and other localizations.

 The technical result from the use of a method for the treatment of locally advanced cancer is that in the combined treatment of patients with locally advanced cancer of the head and neck, as well as other localizations with chemoradiotherapy and operatively, in combination with the prevention and correction of disorders in the immune system, normalization of the total number of leukocytes, lymphocytes and other parameters of the general blood test, stable immunosuppression, severe intoxication (weakness, headaches, dizziness, nausea), the mind is excluded nshayutsya postoperative complications, reduce the increase in pro-inflammatory potential, reduced length of stay in hospital and therefore reduced maintenance and treatment of cancer patients.

 The invention is illustrated in table 1 and 2.

 Example 1. Patient S. 62 years old, Eastball. N 5624 / s. Diagnosis: squamous cell carcinoma of the mucosa of the bottom of the oral cavity with spread to the lower jaw and MTS in L.U. neck. G.a. N 5161-62. Stage III, clinical group 2.

He was admitted with anemia (HB 80, anisocytosis, anisochromia ++), lymphopenia (18 lf), eosinophilia (7), leukopenia (3.8). In the immunogram, a sharp decrease in active and high-affinity rosettes (which is characteristic of tumor processes), changes in the ratios of T _μ and T _γ .
Two days before the start of radiation treatment at 7 a.m., Eleutherococcus extract was started from 25 drops, every 2 days the dose was reduced by 30%. On the 5th day of radiation treatment, there was no lymphopenia (22 lf), but anemia remained (only for hemoglobin), eosinophilia monocytosis appeared (13). A second dose of Eleutherococcus was added, twice the first, after 2-2.5 hours.

 Continues to receive radiation. On the 12th day LF 26, L 5.5, mon 5, but HB 80. After reaching a dose of 5 drops of Eleutherococcus, the scheme was started first, and after 6 days the 2nd dose was connected.

 On the 18th day of exposure: HB 90, L-5.5, LF 26, mon 10, ooz. 5, p. 3. On the 31st day of hospitalization, he received a dose of 40 Gy, the tumor significantly decreased in size (more than twice). HB 114, LF 24, mon - 8, L -4.5.

Given the good effect of the exposure, it was decided to cancel the intended operation and limit the exposure to a radical dose. On the 10th day of radical exposure, the tumor is not detected. Нв 100, лф 22, э 5. In the immunogram, the number of active and high-affinity outlets was normalized, the ratio of T _μ and T _γ ..

 Check after 2 months showed the absence of a tumor both in the oral cavity and on the neck.

 Example 1-a. Patient T. 63 years old, Eastball. N, 2440 / a. Diagnosis: squamous cell carcinoma of the bottom of the oral cavity with spread to the lower jaw, l. slightly enlarged. G.a. N 4511-14. Stage III, clinical group 2.

 He was admitted with leukocytosis (9.0), the rest of the parameters of the blood test are normal, in the immunogram there is a slight decrease in active and high-affinity rosettes, as well as a decrease in RBT on Con A.

 He received radiation in a radical dose without effect, subjectively, the pain decreased. Upon discharge, a further decrease in active and high-affinity outlets, RBT on Con A and on the PHA. Lymphopenia 11, leukocytosis 10.0, n -10.

 Example 1-b. Patient S. 60 years old, source.ball. N 1569 / s. Diagnosis: squamous cell carcinoma of the bottom of the oral cavity with spread to the lower jaw. G.a. N 14598. Art. III, clinical group 2.

 Radiation in a radical dose without effect. He entered the operation with immunosuppression, after the operation, necrosis in the wound lasted more than 26 days. At discharge, necrosis has still not completely passed, lymphopenia 9, monocytosis -13, further strengthening of immunosuppression in all parameters of immunograms.

 Example 2. Patient G. 56 years old, Eastball. N, 7863 / a. Diagnosis: laryngeal cancer with MTS in L.U. neck, stage III, group 3. G.a. N 338965-70: squamous cell carcinoma with keratinization. Concomitant diseases: decompensated diabetes (pastiness, weakness, lost 25 kg in the last 4 months, dry mouth), hypertension (170/90); finger tremor, cyanosis of the face, shortness of breath while walking. Violations of the right ventricle, tachycardia. Severe metabolic disturbances in the myocardium, heart failure II tbsp. respiratory failure II tbsp. chronic bronchitis, emphysema, myocardial dystrophy, chronic pancreatitis.

Upon receipt of leukocytosis, LF 22, the remaining parameters of the blood test are normal. E-sockets and high-affinity sockets are slightly reduced, a decrease in RBT on PHA and Con A, a distortion of the ratio of T _μ and T _γ .

 Received preoperative preparation with appropriate drugs (pulmonary and cardiac). Eleutherococcus extract with 25 drops, every 2 days the dose was reduced by 30% after 5 days, the second dose was added, after 2.5 hours, twice as much as the first.

 Operation: extirpation of the larynx, resection of the root of the tongue, removal of the submandibular salivary gland, fascial-sheath excision of the fiber of the neck.

 6 days after surgery: severe headaches, blood pressure 210/110, suppuration in the wound. Lymphopenia, weakness (9 lf, 1 mc on the 2nd day, 14 lf on the 6th day after surgery). From the 9th day after the operation, the state of health sharply improved (the 7th day of the postoperative reception of Eleutherococcus according to the same scheme), LF 24, everything else is normal. On the 12th day, nutrition through natural ways, the phenomena of necrosis subsided, was discharged with the norm and according to the general analysis of blood, and according to the immunogram. The same eleutherococcus mode is given with it. After 3 months, the condition without relapse, excellent health, concomitant diseases worry less.

 Example 2-a. Patient I. 59 years old, Eastball. N 1304 / i. Diagnosis: laryngeal cancer, l. at. not determined, stage III, group 2. G.a. N 320657: squamous cell carcinoma with keratinization. Concomitant diseases: myocardial dystrophy, possible coronary heart disease, pulmonary heart disease, chronic bronchitis.

 Upon receipt, a blood test is normal (27 lf, 5.6 L, HB 134, etc.). In the immunogram, E-sockets, high-affinity sockets and RBT on PHA are slightly reduced. Received preoperative preparation with cardiac drugs.

 Operation extirpation of the larynx. On the 5th day, suppuration appeared, drainage was placed, receives antibiotics, daily dressings and suction of copious purulent and necrotic masses. Headache, weakness, stoma formed on the 9th day. Discharged on the 18th day with necrosis, a lot of pus, but the volume of soft tissues decreases.

 When discharge lymphopenia 15, left shift (n 12), HB 104. In the immunogram, a further decrease in E- and af-outlets, a decrease in RBT on PHA and Con A.

 Example 3. Patient S. 56 years old, Eastball. N 5227 / a. Diagnosis: laryngeal pharynx cancer, stage III, clinical group 2. G.a. N 331193-44: Squamous cell carcinoma with keratinization. Large tumor with decay.

Upon receipt of leukocytosis -11, left shift (p. 18), LF 23. In the immunogram, the distortion of the ratio of T _μ and T _γ , a decrease in RBT on PHA, an increase in immunoglobulin W, a decrease in E-outlets.

 Operation: extirpation of the larynx and hyoid bone, fascial-sheath excision of the fiber of the neck.

 2 days after surgery, L 17.7, LF 10, fell. 22, HB 98, oligochromia +, anisochromia +. Eleutherococcus extract was prescribed with 25 drops, every 2-3 days to reduce by 30% after 7 days, a second dose was added 2.5 hours after the first twice as much as the first. 8 days after surgery L-5.0, LF 29, fell. 5, no anemia. Repeat the same scheme eleutherococcus after reaching the first dose of 5 drops. The wound heals by primary intention without necrosis. Discharged on the 14th day after surgery in good condition, LF 30, the remaining elements of a blood test are normal. The immunogram is completely normal.

 Example 3-a. Patient A. 56 years old, Eastball. N, 13344 / i. Diagnosis: laryngeal pharynx cancer, stage III, clinical group 2. G.a. N 320056-8: squamous cell carcinoma with keratinization.

 He entered with a normal blood test for all indicators, but with a decrease in the RBT immunogram on PHA and an increase in immunoglobulin J.

 Operation: extirpation of the larynx, fascial-sheath excision of the fiber of the neck.

 On the 12th day after surgery, extensive necrosis in the postoperative wound led to the formation of two fistulas in the chin area. Daily purulent exudate, dressings with antibiotics are removed by electric suction. 21 days after the operation, one fistula closed, the second began to close on the 26th day. Extract on the 27th day after surgery with anemia (HB 92, anisocytosis, anisochromia), L 8.5, eos. 12, fallen. -9, mon. 11. In the immunogram, a further increase in immunoglobulin F, a decrease in immunoglobulin M, a decrease in E-outlets and RBT on PHA. Weakness, headaches.

 Example 4. Patient K. 53 years old, Eastball. N 8523 / i. Diagnosis: relapse of cancer of the lower lip with MTS in L.U. neck. G.a. N 347342-4: squamous cell carcinoma with keratinization.

 Operation: fascial-shear dissection of the fiber of the neck, resection of the lower lip and lower jaw.

 After the operation, extensive necrosis developed, on the 10th day it reached its maximum size, the patient's condition was serious, and therefore therapy with eleutherococcus extract was connected according to the proposed scheme. After 6 days, the wound was completely cleared of necrosis, weakness and headaches disappeared, he was feeling well, no complaints.

 At discharge LF 37, HB 120, L -7.0, all other elements of the blood test are normal, the immunogram is normal.

 Example 4-A. Patient I. 55 years old. source ball N, 1729 / h. Diagnosis: relapse of cancer of the lower lip with MTS in L.U. neck. G.a. N 25564-6: squamous cell carcinoma with keratinization.

 Operation: fascial-shear excision of the fiber of the neck, resection of the lower lip.

 After surgery, extensive necrosis developed and, despite daily dressings, necrotomy, antibiotics and anti-inflammatory therapy, lasted 30 days.

At discharge: lymphopenia 17, fell. -8, anemia (HB 90), monocytosis 12. In the immunogram, a further increase in immunoglobulin W, decrease in immunoglobulin A and M, a change in the ratio of T _μ and T _γ , a decrease in E-ROCK, af-ROCK and active ROCK, but normalization of RBT on PHA and Con A.

 Example 5. Patient M. 58 years old, Eastball. N, 4318 / a. Diagnosis: cancer of the tongue with spread to the bottom of the oral cavity, stage III, clinical group 2. G.a. N 333041: squamous cell carcinoma with keratinization.

 Upon receipt of lymphopenia 13, monopenia 2, aneosinophilia 0, left shift (n 10), leukocytosis 9.6. In the immunogram, the number of active outlets and RBT on the PHA and Con A. is reduced

 Eleutherococcus extract was prescribed with 25 drops in the morning, the daily dose decreased by 30% after 8 days, the second dose was added twice as much as the first.

 Irradiation after a few days caused stress (10 lf), but then the second dose of eleutherococcus was temporarily canceled (mitigation of the effect), and the blood test returned to normal: lf 30.5; eos. 2, L -5.0, the rest is normal.

 After irradiation, the immunogram normalized, the tumor decreased.

 Two weeks later, an extended operation (these two weeks the scheme of Eleutherococcus continued on an outpatient basis), postoperative lymphopenia and anemia were not observed. After the operation, the scheme of Eleutherococcus continued, when the first dose of 5 drops was reached, it started again. A week after the operation, all sutures were removed, the wound is well granulated by primary intention, the immunogram at discharge is normal, lf -30, there is no anemia.

 Example 5-a. Pain K., 58 years old, source ball. N 7096 / a. Diagnosis: cancer of the tongue with spread to the bottom of the oral cavity, stage III, clinical group 2. G.a. N37520: squamous cell carcinoma with keratinization.

Upon receipt of LF 20, fell. 20, L 8.5, in the immunogram, E-ROCK, T _{μ are} slightly reduced, immunoglobulin J. is increased.

 Irradiation on day 4 caused pain in the mouth, weakness. A week later, due to epithelitis, the course was interrupted for 10 days: Analysis: lymphopenia 16, fell. 8, the rest is normal.

 After 10 days he was admitted again, pain and weakness continue, the tumor ulcer is unchanged, food intake is difficult. By the end of the irradiation course LF 18, mon 12, fell. 11, the rest is normal, the tumor has decreased.

 After a month, an operation similar to example 5.

A week after the operation, anemia (HB 90, anisocytosis, anisochromia), L -8.0, severe lymphopenia 4. Extensive necrosis around the postoperative wound, part of the sutures is untenable, serious, plasma transfusion, weakness, pain, poor health lasts 16 days after operations. In this regard, the patient was taken for treatment by the proposed method. After 3 days, LF - 20, HB -140, L 5.0. After another 10 days, discharge was in satisfactory condition: necrosis was significantly reduced, health was significantly improved. Lf 27, no anemia. In the immunogram during discharge, compared with the immunogram 2 weeks before discharge, normalization of previously sharply reduced E-ROCK, A- and af-ROCK, the ratio of T _μ and T _γ , RBT on PHA and Con A.

 Example 6. Patient M, 67 years old, source. N 51731 / a. Diagnosis: squamous cell carcinoma of the bottom of the oral cavity with germination in the oropharynx, mts in L.u. neck. The case is inoperable due to the prevalence of the process, stage III, clinical group 4. Concomitant diseases: coronary heart disease, heart and pulmonary insufficiency II tbsp. obesity, chronic bronchitis and emphysema; no one foot.

 Received with a normal blood test. Polychemotherapy is prescribed. A week later, through PCT, lymphopenia 12, leukopenia 2.8. Eleutherococcus was prescribed according to the proposed scheme. By the end of the course of chemotherapy chemotherapy LF 21, L 4.0. Lymph nodes and swelling in the oral cavity decreased slightly.

 A month later, he was again admitted for radiation therapy. Upon receipt of lymphopenia 9, monocytosis -11, the rest is normal. In the immunogram, E-ROCK, T is slightly reduced, immunoglobulin J. is increased. Eleutherococcus was prescribed according to the proposed scheme. After 9 days, irradiation was discontinued due to radiation epithelitis, but after 4 days the phenomena of inflammation subsided (continued the use of eleutherococcus according to the scheme), radiation was continued. Initially, lymphopenia -8, by the end of the course of irradiation LF 16, L -4.5, the immunogram improved: increase to normal E-ROCK, increase T and T, increase to normal RBT on PHA and Con A, previously increased immunoglobulin M decreased slightly. But there is almost no local effect: the tumor is almost the same size.

 After a month and a half, he was again exposed to radiation, but after a few days the conclusion of the radiologists: radiation has exhausted its capabilities. There is no epithelitis, but the tumor is the same size. The patient was discharged.

 After a month and a half he entered again, all these months he took Eleutherococcus according to the proposed scheme. Analysis at admission: all elements are normal (LF 22, L 6.4, etc.). The tumor is the same size. Polychemotherapy is prescribed. By the end of the chemotherapy chemotherapy cycle, LF -21, L 4.5, the rest is normal, the tumor has decreased significantly, the immunogram is normal.

 Throughout the treatment, well-being and without side effects.

 Example 6-a. Patient M. 53 years old, Eastball. N, 1255 / a. Diagnosis: squamous cell carcinoma of the mucosa of the floor of the oral cavity, mts in L.U. neck. Stage III, group 2. G.A. N 333052.

 Polychemotherapy was prescribed, at the end of the course, subjectively improvement, objectively without effect. Discharged with lymphopenia 12, leukopenia 2.8, aneosinophilia. In the immunogram, an improvement in all respects.

 Example 7. Patient A. 64 years old, Eastball. N, 2525 / a. Diagnosis: thyroid cancer, stage IV. G.a. N 4767-68: follicular cancer.

 During the operation, due to the prevalence of the process, the case was found to be unresectable, but the tumor was maximally excised (not radically).

Before surgery, lymphocytosis 44, leukocytosis 7.0. A week after surgery, lymphopenia 14, left shift -19 fell, leukocytosis 8.6, in the immunogram, the act was sharply reduced. ROCK, af-ROCK, the ratio of T _μ and T _{γ is} perverted, RBT on PHA is slightly reduced, immunoglobulin Zh is increased.

 Eleutherococcus was prescribed according to the scheme for women: starting from 20 drops daily at 7 am, every 2 days reducing the dose by 30% after 7 days, the second dose was added twice as much as the first and 2.5 hours after the first. When the first dose of 3-4 drops is reached, the scheme begins again.

A course of radiation has begun, after a week lymphopenia, but after another 3 weeks lf
22, but monocytosis -15. The immunogram at this time improved: increased to the norm of E-ROCK, almost to the norm of A- and af-ROCK, immunoglobulin J decreased slightly and immunoglobulin M increased, with the norm of immunoglobulin A. By the end of the irradiation course, the tumor disappeared, lph 21, L-4 , 5, HB 125, the rest is normal, further improvement of the immunogram.

 Within a year and a half since then, the patient receives courses of Eleutherococcus according to the proposed scheme, no tumors have been detected yet.

 Example 7-a. Patient G. 51 years old, Eastball. N 3101 / a. Diagnosis: thyroid cancer, stage III. G.a. N 326979-80: follicular cancer.

 The operation is radical.

 Three weeks after the operation, she received radiation and a normal blood test (33 lf, 6 mon. L 4,5; HB 150). By the end of the irradiation course, instead of 40 Gy, she received 36 Gy due to the appearance of hoarseness.

 At discharge, the immunogram deterioration is significant, lymphopenia -10, aneosinophilia, left shift (fallen 15), leukopenia 2.5, anemia (HB 98).

 A few months later relapse.

Claims (1)

 A method of treating locally advanced cancer, including surgical and chemoradiotherapy, characterized in that 2 3 days before the start of treatment and throughout the entire course of any special antitumor treatment, patients receive a fasting every day on an empty stomach, between 7 and 9 hours, starting with the lower therapeutic dose, and every 2 to 3 days, the dose is reduced by 30% from the previous one, and after 5 to 8 days after the start of taking the biostimulator, a second dose of the same biostimulator is added daily, 2.0 2.5 hours after the first dose at a dose of 1.5 to 3 times First, and this course is repeated several times after the first dose of 1/5 lower therapeutic males and 1/7 lower therapeutic in women.

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