A method of treating patients with locally advanced forms of squamous cell carcinoma localized in the mucous membranes of the oral cavity and the oral part of the throat
The invention relates to medicine, in particular to cancer, and can be used for the treatment of patients with cancer of the oral cavity and the oral part of the throat. To do this, first by 2 courses of chemotherapy, including the introduction cisplatin and 5-fluorouracil. Then carry out surgical treatment, while after performing intraoperative spend bolus deposition of 5-fluorouracil in the field of primary tumor through the corresponding branch of the external carotid artery before removing this center. Re-produce pick 5-pierorazio in the bed of the removed tumor and simultaneously hold the plastic postoperative defect of the two flaps: mucoperiosteal flap against the hard palate, complex arterialization skin-muscle flap, including the pectoralis major muscle, which are under the collarbone. The method improves the effectiveness of chemotherapy, elasticnet surgery reduces postoperative complications and complications during the initial functional rehabilitation of patients. 6 silt.
The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with metersper with locally advanced tumors of the mucosa of the oral cavity and the oral part of the throat, includes radiation therapy and surgery in various combinations (PABSEC A. I. - Tumors of the head and neck. - M.: Medicine, 1997, S. 142-177, 329-340).
However, the method is ineffective and causes lots of complications.
The closest achieved a positive result (the prototype) is a method of treating patients with locally advanced forms of tumors of the mucosa of the oral cavity and oropharynx, which is to assign chemotherapy by intravenous cisplatin at a dose of 100 mg/m2on day 1 of each treatment course of 5-fluorouracil at a dose of 1000 mg/m22 through day 6 (2 courses), and in the second stage of the combined treatment of surgical intervention, with subsequent courses of radiation therapy at a dose of 40-46 GY. (Cicmanec H. W. Malignant tumors of the head and neck. - ,Tomsk, 1998, S. 122-143).
However, the known method is ineffective and there is a high frequency of complications of chemotherapy and postoperative period.
The authors propose a new and effective method of treating patients with locally advanced forms of tumors of the mucosa of the oral cavity and oropharynx, which consists in stage-by-stage treatment: chemotherapy, surgical volatileimage results of the proposed method is to improve the effectiveness of treatment by increasing the effectiveness of chemotherapy, increase elasticnet surgical intervention, reducing the number of postoperative complications and primary functional rehabilitation of patients.
A positive result is achieved that in the first stage of the combined treatment of 2 courses of neoadjuvant intra-arterial regional chemotherapy: cisplatin at a dose of 100 mg/m on day 1 of each treatment course of 5-fluorouracil in the form of a 6-hour infusion at a dose of 750 mg/ m22 through day 6 of each course, at the second stage of the combined treatment to one-stage surgical intervention on the routes of lymphatic drainage and primary tumor site, with intraoperative deposition of chemotherapy into the tumor bed, and in the third step are conducted simultaneously plasticity defect oropharyngeal area complex arterialization skin-muscle flap or a combination of scraps.
The proposed method is as follows.
The treatment is carried out in stages:
Phase I: conduct patient 2 polychemotherapy,
Stage II - simultaneous extended-combined surgery with intraoperative 2-fold deposition of chemotherapy before resection of the primary lesion and in the bed of the removed tumor.
III stage - one therapy.
The first stage of policythere includes the introduction of two drugs:
1) cisplatin at a dose of 100 mg/m2on the background of fluid overload on the first day of each course, intraarterially, which is injected through a catheter in one case in the superficial temporal artery, the other through the occipital artery (Fig.1);
2) 5-forall at a dose of 750 mg/m2that is administered to the patient on day 2-6 of each course by a long 6-hour intra-arterial infusion.
The infusion is carried out with the help of a dispenser of drugs “Lineout”, in KARL-MARX-STADT).
Stage II. After treatment is 2-3 weeks after edema adverse reactions patients spend extended-combined surgery on InfoPath neck and primary tumor site. After processing the surgical field on Grossao under local infiltration anesthesia S. Nov. 0,25% - 30 ml perform a tracheostomy without crossing the isthmus of the thyroid gland. After performing tracheostomy perform premedication: atropine, diphenhydramine, Relanium and promedol in standard dosages. Then hold anaesthesia induction: ketamine, a short-acting muscle relaxants. The intubation produced through a tracheostomy. Basic anesthesia p is algesia (fentanyl+Relanium+droperidol) in the standard dose per 1 kg of body weight over time. After giving basic anesthesia consistently perform surgery on InfoPath neck and the base of the lesion (Fig.2). Intraoperative produce bolus deposition of drugs in the field of primary tumor by catheterization of the corresponding branch of the external carotid artery after preliminary ligation of the external carotid artery, facial veins, pharyngeal veins before removal of primary tumor. Make a Deposit of 5-fluorouracil at a dose of 250 mg/m2(Fig.3). Perform electroresection tumors. Re-produce the deposition of 5-fluorouracil at a dose of 250 mg/m2in the bed of the removed tumor (Fig.4). The catheter is removed.
Stage III - plastic postoperative defect oropharyngeal area complex arterialization skin-muscle flap, which includes a large chest, sternocleidomastoid or trapezius muscle (depending on the amount of tissue removed). In some cases, for plastics large defects (Fig.5) use a combination arterializing skin and muscle and mucoperiosteal flap with the hard palate), in most cases, the flap with the insertion of the pectoralis major muscle is carried out in the neck under the collar (Fig.6), which eliminates the compression of the vascular pedicles lo the material effect of lengthening it and corrects cosmetic defects in the form of additional volume of the soft tissues in the region of the clavicle and the lateral surface of the neck.
3-4 weeks after complete surgical intervention in patients spend beam photon therapy in the aftercare plan. Perform photon irradiation with gamma-therapeutic setting “Rocus-M with an average energy of irradiation With 60 to 1.4 MEV, a single dose of photon radiation is 2.0 Gy, radiation treatment 5 times a week, total dose reaches 40-46 Gy.
Patient Izvekov C. N., 60, male, treated in the Department of head and neck tumors since April 2000, case history No. 22456. Diagnosis: cancer of the mucous membrane of the oral part of the throat to the right T4N1M0. D. No. 2459, 13.04.00, squamous orogovevshi cancer. The surface area of the patient's body was 1.7 m2. Objectively before treatment the patient was determined ulcero-infiltrative form of growth of the tumor occupying the right retromolar region, anterior palatal bow, mandlikova niche and the velum amygdala, posterior palatal bow, extending to the right side of the soft palate, the mucous membrane of the floor of mouth right in posterior third, at the root of the tongue to the right. It was noted the limited mouth opening, up to 2 cm, which indirectly indicates the spread of the tumor in the internal pterygoid muscle on the right.
With 21.04.00, 27.04.00, a course of intra-arterial regional chemotherapy: cisplatin 170 mg day 1 simultaneously on the background of overhydration (100 mg/m2), 5-fluorouracil by protracted six-hour intra-arterial infusion from the second to the sixth day, a total dose of 5.5 g (1,000 mg/m2). 24.05.00) underwent catheterization of the external carotid artery to the right access via the superficial temporal artery on the right. With 24.05.00, 29.05.00, the patient received 2 courses of policythere a similar program. The total dose of chemotherapy received by patients during the second year, were the same as in the first course.
After the chemotherapy in the survey was determined residual tumor mixed growth form, occupying the front of the palatal arch, part of the tonsils.
Effects after chemotherapy is over 50%. In the process of chemotherapy, the patient developed complications such as recurrent aphthous stomatitis and alopecia corresponding regional blood flow to the scalp in the occipital region and superficial temporal arteries.
3 weeks after the end of chemotherapy side effects were cropped. 27.06.00, patient had the operation I fasciale-casing excision of tissue of the neck to the right, given the area the location of the tumor, after preliminary ligation of the external carotid artery above the level of the discharge verkhnestepnoi artery produced ligation and catheterization of the barrel lingual artery. Made a Deposit of 5-fluorouracil at a dose of 250 mg/m2. In a single block is executed electroresection retromolar region, anterior palatal arch, the tonsils, posterior palatal arch together with the right side of the soft palate, the internal pterygoid muscle, 1/2 of the tongue root, the bottom of the mouth. Simultaneously performed through resection of the body and the branches of the lower jaw from the articular ridge right before the 1st premolar of the lower jaw to the left. Re-produced by deposition of 5-fluorouracil at a dose of 250 mg/m2in the bed of the removed tumor. The catheter is removed. D.: No. 2072/8, 4.07.00, - usernotification squamous cell carcinoma, metastasis in one lymph node. The resulting soft tissue defect oropharyngeal area was compensated for by using a combination arterializing skin-muscle flap with the insertion of the pectoralis major muscle and mucoperiosteal flap against the hard palate, the flap with the insertion of the pectoralis major muscle was performed in the neck under the collar and under the sternocleidomastoid muscle. The wound healed CPS 7.09.00, patients received a course of postoperative gamma-therapy, single focal dose was 2 Gy, 5 times per week, total - 40 Gr. Radiomedical was carried out by introduction of 5-fluorouracil at a dose of 500 mg/twice a week. Complications of radiation therapy: catarrhal epithelitis at a dose of 38 Gy.
The proposed method only treated 22 patients (19 men and 3 women), aged 45 to 70 years. All patients had common forms of tumors IIIB-IV century, localized in the mucous membranes of the oral cavity - 4 patients, in the field of language - 6 patients, the alveolar bone of the upper jaw - 2 patients, oropharyngeal - 10 patients. All patients were conducted on 2 courses of polychemotherapy according to the proposed scheme. The efficiency was: complete regression of the tumor was achieved in 33% of cases (7 patients), partial regression of the tumor was recorded in 56% of cases (12 patients), stabilization was 11% (3 patients).
The progression was not observed in a single patient.
Patients received 44 polychemotherapy, during which noted the following complications: nausea/vomiting I-II grade - 12 courses, grade I-II grade - 8 courses, stomatitis - 18 courses, alopecia developed in 14 pain is oxitest was lower than standard courses of systemic chemotherapy.
At the 2nd stage of a combined treatment of all patients was carried out surgical treatment in various volumes, including intraoperative deposition of chemotherapy according to the described method.
In all cases, managed to perform radical surgery. In 8 (36% of patients) performed simultaneous plastic defect complex arterialization skin-muscle flaps or mucoperiosteal flaps, in 2 cases used a combination of data types of plastics (clinical example).
Postoperative complications developed in 3 (13,6%) patients, 1 patient - gapping, healing by second intention with the formation of urostomy, in 2 patients gaping wound healing by second intention with the formation of orovada, which subsequently closed independently and did not require any additional actions.
At the last stage of treatment, all patients received a course of distance gamma-therapy in the postoperative plan of SOD 40-46 Gy depending on the extent of the process according to TNM using as radiomodifying 5-fluorouracil at a dose of 500 mg two times per week.
T the economic institutions, engaged in comprehensive treatment of patients with tumors of the oral cavity and the oral part of the throat.
A method of treating patients with locally advanced cancers of the mucous membranes of the oral cavity and the oral part of the throat, which is to assign chemotherapy, including regional intraarterial introduction cisplatin at a dose of 100 mg/m2on the first day of each course and 5-fluorouracil at a dose of 750 mg/m22 through day 6 of each course and conduct of 3-4 weeks of surgery, followed by radiation therapy, characterized in that an additional 5-fluorouracil is administered intraarterially by prolonged 6-hour infusion and during surgical treatment carried out twice intraoperative bolus deposition of 5-fluorouracil in the tumor bed in stages: after complete lymphadenectomy by catheterization the corresponding branch of the external carotid artery after preliminary ligation of the external carotid artery, facial veins, pharyngeal veins before removal of primary tumor and after removal in the tumor bed and simultaneously conduct primary surgical rehabilitation by plastics postoperative defect combination of the flap to hold the flap with the insertion of the pectoralis major muscle under the collarbone.
where R1, R2and R3are H, HE or och3group and R4represents the following groups:
The proposed pharmaceutical composition having antitumor activity, containing at least one derivative of 5-imino-13-deoxy of anthracycline
where the values of A, B, K, T, W, X, Y, U, V, Z, R1specified in paragraph 1 of the claims