The method of treatment of lung cancer
The invention relates to medicine, in particular to cancer, and can be used in the treatment of resectable, including locally common forms of lung cancer. The method includes radical surgery and autohemotherapy. While on the operating table, before the introduction of anaesthesia, produce blood of the patient in the amount of 150-200 ml in a sterile bottle with a solution of Pulizia” and enter it anticancer drugs in standard single or exceeding their doses. Produce incubation of chemotherapy with Autocraft during administration the patient in anaesthesia and start reinfusion patient autologous blood with chemotherapy prior manipulation of the tumour lung, continuing to perform the major phases of the operation during 1-1,5 hours. In the postoperative period according to the testimony spend radiation therapy. The method allows to prevent hematogenous metastasis in surgical treatment of lung cancer due to chemotherapeutic effect on entering the bloodstream tumor cells prior to their implantation in the absence of side effects of chemotherapy.
The invention relates to medicine, in catform lung cancer.
There is a method of cancer treatment, which consists in the introduction of anticancer chemotherapy, United with the blood of the patient, autohemotherapy.
The method is effective and has better tolerability compared with systemic introduction of anticancer chemotherapy. It is well established in the treatment of malignant neoplasms of different localization. Autohemotherapy often used as pre-exposure, with the aim not only to reduce the size of the tumor and thereby to improve the conditions of operation, but also the damage of tumor cells, reduce the risk of hematogenous metastasis when injected these cells into the blood stream when the manipulation of the tumour body during surgery. At the same time, this method has the major drawback of a rather long interval between the beginning autohemotherapy and operation: the duration of neoadjuvant course - 2 weeks, the recovery period is 2 weeks. Thus, potentially resectable patients intervention is delayed for about a month. It's better than when neoadjuvant systemic exposure similar to that which the interval is 1.5-2 IU the l during this time can be irresectable, while the individual cells, completely restored, is to give hematogenous metastases.
A known method of performing pneumonectomy for lung cancer (Patent No. 2163465 And 61 In 17/00. Bull. No. 6 from 27.02.2001), chosen as a prototype, characterized in that to prevent hematogenous metastasis during surgery, the first stage produces vnutriarterialno the capture of pulmonary vessels at the turnstiles and crushing them. This contributes to the termination of pulmonary blood flow in lung removed and the remaining stages of the operation, the tumor cells are mechanically unable to enter the systemic blood stream.
The disadvantage of this method is a technical impossibility of its application for standard operations, the volume of which is less than pneumonectomy (segmental resection, lobectomy, bilobectomy) handled the vessels are outside the pericardium. In addition, in order to approach the pericardium, open it, highlight and take the turnstiles pulmonary vessels, you must first make pneumonia (emphasis lung adhesions, including the separation of the light from the pericardium), and perform an audit to determine the resectability of the process and the volume of transactions. It is at this e the STU to prevent hematogenous metastasis. The proposed method should be used with caution in the elderly and patients with concomitant cardiac pathology, because the opening of the pericardium and vnutrepenialnye manipulation can cause abnormal heart rhythm or even stop him.
The aim of the invention is to prevent hematogenous metastasis in surgical treatment of lung cancer.
This objective is achieved in that on the operating table before the introduction of anaesthesia produce blood of the patient in the amount of 150-200 ml in a sterile bottle with a solution of Pulizia” and enter it anticancer drugs in standard single or exceeding their doses, during the introduction of the patient to the anesthesia and perform a thoracotomy for 30-40 minutes makes the incubation of chemotherapy with Autocraft since opening the chest cavity before manipulation of the tumour lung, the patient begin reinfusion autologous blood with chemotherapy and continue to perform the major phases of the operation during 1-1,5 hours, according to indications in the postoperative period perform radiation therapy.
The invention is a Method of treatment of lung cancer” is new, because it is not the proposed method with known used for the treatment of patients with lung cancer showed that the proposed method is new, as it provides for intraoperative course autohemotherapy - transfusion of autologous blood, incubated with anti-tumor chemotherapy. This allows powerful chemotherapeutic effect on the fall in systemic circulation tumor cells prior to their implantation and thereby prevent hematogenous metastasis. With significant local process prevalence of lung cancer in the postoperative period intraoperative autohemotherapy combined with carrying out the conventional radiation treatment, as regardless of pre - or intra-or postoperative chemotherapy, the risk of local recurrence is quite high.
In the available sources of information Russia, CIS and abroad indication of the proposed method for preventing hematogenous metastasis at the time of surgical intervention was not found.
The proposed method is industrially applicable, as it can be repeated many times in the treatment of lung cancer patients in specialized and therapeutic criteriological confirmed diagnosis of lung cancer prior to surgery, including on the operating table before the introduction of anaesthesia, produce blood in quantities of 150 -200 ml in a sterile bottle with a solution of Pulizia” and enter it anticancer drugs in standard single or exceeding their dosages (500 mg/m2of cyclophosphamide 500 mg/m25-fluorouracil 500 mg/m2of cyclophosphamide and 25-30 mg/m2doxorubicin or other combinations). During administration the patient to the anesthesia and perform a thoracotomy (30-40 minutes) is produced by incubation of chemotherapy with Autocraft by the standard method. At the moment of opening the chest cavity, prior to manipulation of the tumour lung, the patient begin reinfusion autologous blood with chemotherapy, which continues to perform the major phases of the operation - pneumonia, audit, selection and treatment of pulmonary vessels, bronchus, removal of the drug, for 1-1,5 hours. Completes the operation is standard. In the postoperative period can be shown to be held chemo - or radiation therapy.
The method is tested in the surgical treatment of more than twenty patients with lung cancer I-III stages, which was performed operations in the amount of from lobectomy to an advanced combination of pneumonectomy method can serve as a statement of case histories.
1. B th T to C. D., 72 years, the case history No. 20719/O.
Diagnosis: cancer of the lower Central lobe of the left lung stage IA (pT1N0M0) CL gr. 2.
Radiograph of the patient in the lower lobe of the left lung is detected tumor node associated with the root of the lung. The lower lobe of the left lung lower pneumatization. On the tomogram - tumor peribronchial extends to the proximal bronchus. Bronchoscopy revealed a tumor involvement of proximal bronchus. Histologically verified moderately differentiated squamous cell carcinoma. When examining a patient data on the presence of distant metastases is not received. It was decided to perform surgery. The operation took place - the lower left lobectomy. Directly on the operating table, the patient made a fence 200 ml of blood, and incubated with it for 40 minutes at a temperature of 37°With 1000 mg of cyclophosphamide and 1000 mg of 5-fluorouracil, and then she repusively the patient during surgery. During surgery and anesthesia smooth. In the early postoperative period, nausea, vomiting, diarrhea and other other peculiar chemotherapy complications were noted.
On the 2nd day of the postoperative period bomme the remaining part of the left lung is expanded, there are small pleural overlay above the diaphragm.
Taken two weeks after the surgery, tests showed that the biochemical, hormonal and immunological data of the patient is fully normalized in comparison with the original.
Given the relative proximity peribronchiolar component of the tumor for resection proximal bronchus, the patient starting from 2 weeks of the postoperative period started radiotherapy 2 Gy, 5 times a week to SOD-40 Gr. Usually radiation treatment for 3-4 weeks after surgery. Treatment the patient underwent fine. Discharged in a satisfactory condition. Is under observation. Data for the presence of recurrence or distant metastases no.
2. B th f s centuries, 67 years old, medical history, 1720 /R.
Diagnosis: primary multiple cancer: 1) cancer of the lower lip stage II, the state after the combined treatment (surgery + radiation therapy) in 1996, relapse in 1997, the state after the second surgery and radiotherapy CL gr. 3. 2) peripheral cancer of the lower lobe of the left lung with centralization stage IIIA (R. T2N2M0) CL gr. 2.
During examination: the patient is fully reiterova lower lip. Data for recurrence not the bedroom with segmental bronchi. The left root is not differentiated due to the presence of metastatic lymph nodes. On the tomogram tumor affects6and growing up to the proximal bronchus. Data on patients with distant metastases is not received.
On the background of intraoperative autohemotherapy produced pulmonectomy left with mediastinal lymph node dissection. Blood from the patient was taken to the operating table, incubated with cyclophosphamide (1000 mg) and 5-fluorouracil (1000 mg) and reinfusion during surgery. During surgery and anesthesia smooth. Postoperative nausea, vomiting and other complications were noted. The wound healed per primam. Sutures were removed on day 7. Histologically verified squamous cell carcinoma with foci of necrosis in lymph nodes revealed metastatic cancer. Clinical, biochemical and immunological tests are normal.
The patient was discharged from hospital in satisfactory condition. In the following recommended radiation therapy.
Technical and economic efficiency “method of treatment of lung cancer” is
- in the prevention of hematogenous metastasis of lung cancer, by the direct impact of chemotherapy on circulating in the blood is directly during the operation, instead of 3-4 weeks, as this is carried out by standard methods;
intraoperative conduct autohemotherapy not accompanied characteristic of chemotherapy, diarrhoea or other complications, which leads to improving the quality of life of patients;
intraoperative transfusion of autologous blood with chemotherapy allows in some cases to refuse transfusion of donor blood;
- improves the immune status of patients, due to the stimulating effect of autologous blood transfusion.
A method of treating lung cancer, including radical surgery and autohemotherapy, characterized in that on the operating table, before the introduction of anaesthesia, produce blood of the patient in the amount of 150-200 ml in a sterile bottle with a solution of Pulizia” and enter it anticancer drugs in standard single or exceeding their doses, produce incubation of chemotherapy with Autocraft during administration the patient in anaesthesia and start reinfusion patient autologous blood with chemotherapy prior manipulation of the tumour lung, continuing to perform the major phases of the operation during 1-1,5 h; in posleoperatsi the
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
or its pharmaceutically acceptable salt
where: A means-OR1-C(O)N(R1R2or-N(R1R21; each X, Y and Z independently represents N or C(R19); each U represents N or C(R5), provided that U is N only when X represents N, and Z and Y denote CR19; each W represents N or CH; V denotes: (1) N(R4); (2) C(R4)H; or (3) the groupdirectly related to the group -(C(R14R20)n-A,denotes a 5-6-membered N-heterocyclyl, optionally containing 6-membered ring additional heteroatom selected from oxygen, sulfur and NR6where R6denotes hydrogen, optionally substituted phenyl, 6-membered heterocyclyl containing 1-2 nitrogen atom, optionally substituted 5-membered heterocyclyl containing 1-2 nitrogen atom, aminosulfonyl, monoalkylammonium, dialkylaminoalkyl,1-6alkoxycarbonyl, acetyl, etc