RU2268724C1 - Method for treating oncological patients with vaginal tumor lesion - Google Patents

Abstract

FIELD: medicine, oncology.

SUBSTANCE: one should carry out chemoradiation therapy at applying a cytostatic preparation followed by distance and intracavitary irradiation. Depending upon development of tumor lesion during the first 3 or 6 d it is necessary to conduct monochemotherapy only due to introducing proxiphen together with dimethyl sulfoxide at weight ratio of 4.5-5.0 : 0.5-1.5, correspondingly by applications in "Coletex" napkins. Moreover, a napkin should be pre-impregnated in 20%-dimethylsulfoxide solution and fixed with a tough vaginal tamponade by changing napkins every 24 h. Then since the 4^th d or the 7^th d simultaneously with application it is necessary to carry out contact irradiation and distance impact onto minor pelvis every 4-6 h at single focal dosage (SFD) being 2 Gy at 10 seances 5 times/weekly with high-activity sources of SFD 2 Gy. The innovation provides tumor regress under conditions of no therapeutic complications, thus, improving patients' quality of life.

EFFECT: higher therapy.

3 ex

Description

The invention relates to medicine, namely to oncology, and can find application in the treatment of predominantly common gynecological cancer, burdened by an extended tumor lesion of anatomical structures adjacent to the primary tumor focus, which makes it impossible to implement radical treatment programs.

Patients with an extended vaginal lesion are one of those groups where the possibility of special treatment of both combined and radical combined radiation therapy is sharply limited due to the significant volume of tumor lesion, the true borders of which significantly exceed visually determined, violations of the natural topography of the pelvic organs, and adequate tumor blood supply due to spontaneous destruction and a relative decrease in radiosensitivity in conditions x hypoxia.

Radical combination radiation therapy based on the alternation of remote and intracavitary radiation therapy continues to remain a well-known method of treating advanced gynecological cancer for several decades. (A.M. Granov, V.L. Vinokurov. Radiation therapy in oncogynecology and oncourology. St. Petersburg. Publishing house "Foliant". 2002, S. 166-168).

In 2/3 of the patients of the described category with an SOD of 20 Gy, the regression level necessary to start intracavitary gamma-therapy (HPVT) cannot be achieved. Submucosal infiltration of the arches and walls of the vagina, tumor masses on the mucous membrane of the vaginal tube, rigidity of the walls of the vagina, its frequent stricture hinder the timely initiation of intracavitary irradiation with adequate placement of endostats, require significant dose reduction from HPT, which reduces the overall therapeutic effect. In a third of patients, only palliative radiation programs are implemented, in 20% of patients, due to the lack of conditions for HPT, they have to limit themselves to conducting only remote radiation.

A known method of treating cancer patients with tumor lesions of the vagina, including chemoradiotherapy using cytostatics, remote and intracavitary radiation (Gorbunova V.V. "Optimization of combined radiation therapy of locally advanced cervical cancer and relapse of ovarian cancer with chemotherapy in therapeutic mode" Diss. Academician, Doctor of Medical Sciences, M., 2002, p. 91, prototype).

The effectiveness of the method for the described category of patients is insufficient, since the proposed radiation doses with the simultaneous administration of cytostatic intravenously are of limited use in patients with concomitant pathology and impaired renal function, liver, cardiovascular system, and in some cases lead to significant hematological, gastrointestinal, urological complications , the cost of escort drugs is high and inaccessible to many patients.

The technical task of the present invention is to develop an effective and at the same time gentle treatment for cancer patients with vaginal lesions, which in some cases allows for a course of radical combined radiation therapy without severe reactions and complications due to an increase in the rate and volume of tumor regression and the timely emergence of conditions for adequate HPVT or other radical / conditionally radical therapy programs.

For this, in the method of treating cancer patients with tumor lesions of the vagina, including chemoradiotherapy using cytostatics, remote and intracavitary irradiation, it is proposed to conduct monochemotherapy only during the first 3 or 6 days, depending on the spread of the tumor lesion, while taking local chemotherapy (local) cytostatics apply the application with a Coletex napkin with proxypheine and dimethyl sulfoxide added in a mass ratio of 4.5-5.0: 0.5-1.5, respectively, at m preliminarily wet the napkin with a 20% solution of dimethyl sulfoxide and fix it with a tight tamponade of the vagina, change the napkin every 24 hours, from 4 or 7 days carry out irradiation simultaneously with the application, including contact irradiation with sources of high activity of ROD 2 Gy and remote radiation the impact after 4-6 hours on the pelvis ROD 2 Gy 10 sessions, 5 times a week.

For primary patients with cervical cancer with tumor lesions of the vagina, then continue treatment with combined radiation therapy in radical doses.

The choice of the drug "Proxyphein" is due to the correspondence of the obtained experimental data to a number of requirements for the choice of a cytostatic agent, which, when used in combination with a significant amount of radiation, should have its own high antitumor activity, moderate general toxicity, especially hematological and gastrointestinal, not cause ulcerative necrotic changes in adjacent healthy tissues with prolonged contact, in the used concentrations possess radio modifiers effect, potentiating the antitumor effect of ionizing radiation.

The Koleteks napkins we used were a textile base with a layer of dimethyl sulfoxide and an antitumor drug proxyfein applied to it. Proxyphein is a derivative of caffeine - gamma dimethyl aminopropyl ether hydrochloride 8-hydroxycaffeine. According to the mechanism of action, it is a cytostatic (antimitotic) drug from the class of antimetabolites of nucleic acid metabolism. Proxyphein inhibits the activity of cyclic adenosine monophosphate phosphodiesterase (cAMP), which leads to an increase in the intracellular concentration of cAMP, one of the natural compounds that control cell proliferation and differentiation. Proxyphein causes significant changes in the generation cycle of tumor cells, which consists in lengthening the cycle (especially its presynthetic and synthetic phases) and in delaying the transition of cells to the postsynthetic phase.

The use of proxyphein in the form of the Coletex therapeutic complex containing a biocompatible sodium polysaccharide-alginate polymer and cytostatic applied to a textile base (tissue), with its application, makes it possible to achieve a selective prolonged chemotherapeutic effect on the tumor at an average therapeutic dose with a minimum general toxic effect due to the lack of significant absorption of the drug into the bloodstream with the application method of administration. When combining local prolonged MCT with proxyphein with radiation therapy in the previously described mode, the radiomodifying effect of the used cytostatic is also demonstrated, while the rate and volume of tumor regression increase significantly.

To date, the proposed method has treated 14 women who have been found to be uncurable during initial treatment. All were diagnosed with locally advanced genital tumors with vaginal tube lesions and destruction of the vaginal portion of the cervix (cervical cancer - 8 women, uterine cancer - 3, vaginal cancer - 1, ovarian cancer - 1, colon cancer - 1). Carrying out the proposed method at the first stage of treatment, it was possible for all patients to achieve a significant positive effect - partial regression of the tumor along the vaginal tube with the resolution of the tumor stricture of the vagina, the formation of the vaginal portion of the cervix, as a result of which conditions appeared for conditionally radical and palliative in this group of patients special treatment programs. In general, the treatment was effective in 80% of women: a complete clinical and cytological primary cure was achieved in 30% of patients, they are all alive with no signs of progression at present, the follow-up period was from 18 to 24 months. Partial regression was achieved in 50% of patients, the time to disease progression was from 4 to 24 months, while progression in the irradiation zone was detected in only one of them.

The essence of the proposed method is illustrated by clinical examples.

Example 1

Patient D.O. A., born in 1955, medical history N 4496 \ 2, was admitted to the hospital with suspected vaginal tumor.

A comprehensive examination revealed stage IIIb cervical cancer (T3bNxMo), a vaginal-parametric variant with the spread of the tumor process to the vagina to the lower third, the development of its complete stricture, involvement of parameters on both sides, and pelvic lymphadenopathy. Kolporragia. Anemia 2 tbsp. Impaired function of both kidneys 3-4 degrees.

Morphological diagnosis: No. 3023-4 \ 02 - squamous cell carcinoma.

Accompanying illnesses; Ischemic heart disease. Hypertension of the 2nd stage, crisis course, NK 1-2. Type 2 diabetes mellitus, moderate. Chronic calculous cholecystitis. Obesity 3-4 degrees.

Consulted by a chemotherapist, PCT is impractical due to gross renal impairment.

Given the extent of the lesion and the somatic status of the patient, initially the patient was scheduled for symptomatic - hemostatic - radiation therapy.

Along with a comprehensive examination, the patient began to apply a Coletex napkin moistened with a 20% solution of dimethyl sulfoxide containing proxypheine and dimethyl sulfoxide in a mass ratio of 4.5: 0.5 to the tumor at the entrance to the vagina. The napkin was fixed with a gauze swab that was inserted into the vagina to the maximum possible depth (the first day - 1.5 cm, after 2 days - 3 cm). Napkins were changed every 24 hours. By the 3rd day hyperemia, fibrinous films on the surface of the tumor appeared, the tumor softened somewhat by palpation, the length of the vaginal stricture decreased (tamponade was already at a depth of 3 cm). By 6 days, the depth of the vaginal tube was 4 cm, a moderate hemostatic effect was noted in the form of termination of non-contact spotting from the vagina, which allowed starting radiation therapy from the 7th day, which included contact irradiation using a colpospost on the AGAT-VU apparatus with Co- 60 high activity, ROD of 2 Gy on the surface of the colpostat (which corresponded to 250% -200% isodose), with the number of positions of the radiation source corresponding to the maximum length of the vaginal tube (on day 7 - 4 positions, on day 19 - 8 positions), and distance ion radiation therapy (DLT) at the 6-MeV LUE, the sessions of which were carried out on the same day as contact irradiation, 4 hours later, from 2 opposite fields of 18 × 20 cm, with the lower border of the field 1 cm below the entrance to the vagina , ROD 2 Gy on the basin. Thus, the daily dose to the vaginal tube was 4 Gy, in the center of the pelvis - 2 Gy. The proxyfein applications in the form of Coletex napkins were not interrupted: the napkin was removed for the duration of the contact irradiation session, after which it was again applied, folded in half, with the sides containing the cytostatic agent, to the tumor-like front, back wall and dome of the vagina, fixing the gauze swab located between the front and back sheets of napkins. On weekends, when irradiation was not carried out, the change of wipes was made every 24 hours in the above manner. In total, 10 irradiation sessions were carried out as described above, with the irradiation rhythm 5 times a week. The total dose from all types of radiation by the end of the stage was 20 Gy in the center of the pelvis, 40 Gy per vaginal tube. The number of proxyphein applications was 20.

With a gynecological examination at the end of treatment in this way: the vulva with moderate hyperemia. Edema, desquamation of the epidermis is not observed. The vaginal tube 8 cm long, it was possible to examine the cervix in the mirrors - its vaginal portion up to 6 cm in D, formed, coarse-lumpy, with uneven contours, does not bleed contact. The body of the uterus is enlarged due to the myomatous node to 14 weeks, the appendages are not clearly palpable due to obesity. Infiltrate in the left parametrium almost to the pelvic wall, in the right is preserved cervically. Discharges are serous, scanty.

Expressed positive results were achieved: hemostatic effect, a 1.56-fold decrease in tumor volume according to ultrasound and x-ray computed tomography, with resolution of the vaginal stricture, the emergence of conditions for intrauterine gamma therapy. The patient changed the plan for further treatment - from symptomatic to conditionally radical chemoradiotherapy. A complete primary cure has been achieved. During follow-up examinations in December 2002, February, May 2003, and April 2004, no data were obtained for the progression of cancer. The quality of life corresponds to 1 tbsp. ECOG violations.

Thus, due to the treatment in this way, a patient with locally advanced stage IIIb cervical cancer, recognized at the beginning of therapy as incurable, that is, not subject to special treatment, is alive without relapse for 1.5 years with a good quality of life.

Example 2

Patient G. A.M., born in 1933, case history No. 3051, was admitted to the clinic in 2002 with a diagnosis of Cervical Cancer IIb (T2bNxMo) st. Condition after combined radiation therapy in 1993. Progression. Vaginal metastases, inguinal lymph nodes. Kolporragia.

Morphological diagnosis No. 2345-7-8: squamous cell carcinoma of moderate differentiation.

Concomitant diseases: Atherosclerotic cardiosclerosis. Calculous cholecystitis. Cyst of the left kidney. Varicose disease of the lower extremities.

A comprehensive examination of a patient 70 years old 10 years after radical combined radiation therapy for cervical cancer IIb (T2bNxMo) Art. The progression of the tumor process, metastases in the vagina with the development of incomplete stenosis, heavy bleeding from the vessels of the tumor, metastases to the inguinal lymph nodes were established. Somatic status reduced to grade 3 ECOG. The possibilities of special treatment are significantly limited (inoperable, PCT has been denied due to gross renal impairment, the reserves of radiation therapy are small, and the technical conditions for contact radiation therapy are absent).

The patient began to bring proxyphein cytostatic to the vaginal tumor, for this Coletex napkin moistened with 20% dimethyl sulfoxide solution containing proxypheine and dimethyl sulfoxide in a mass ratio of 5.0: 1.5, folded in half, the sides containing the cytostatic were applied to the tumor-modified anterior , the back wall and the dome of the vagina, tightly fixed its position with a gauze swab, located between the front and back sheets of the napkin, through a tight tamponade of the vaginal stump. Napkins were changed every 24 hours. By the 3rd day hyperemia appeared, a significant number of fibrinous films on the surface of the tumor in the dome, the tumor at the entrance palpated somewhat softened, the length of the vaginal stricture decreased (tamponade was already 3 cm deep), a moderate hemostatic effect was noted in the form of termination of non-contact spotting from the dome vagina, which allowed to start radiation therapy from the 4th day taking into account the reserves of tolerance, which included contact irradiation on the apparatus "AGAT-VU" with high activity Co-60 sources using thin o colpostat, ROD 2 Gy on the surface of the colpostat (which corresponded to 250% -200% isodose), with the number of positions of the radiation source corresponding to the maximum length of the vaginal tube (4-5 positions), and remote radiation therapy (DLT) on the LUE 6 meV, sessions of which were carried out on the same day as contact irradiation, after 4 hours, from 2 opposite fields of 10 × 15 cm, with the lower border of the field 1 cm below the entrance to the vagina, genus 2 Gy per pelvis. The daily dose to the vaginal tube was 4 Gy, in the center of the pelvis - 2 Gy. The proxyfein applications in the form of Coletex napkins were not interrupted: the napkin was removed for the duration of the contact irradiation session, after which it was again applied as described above. The total number of radiation sessions was 10.5 times a week, the total dose from all types of radiation by the end of the stage was 20 Gy in the center of the pelvis, 40 Gy per vaginal tube. The number of proxyphein applications was 20.

The effect is favorable, the cessation of bleeding is noted, partial regression is achieved (a decrease in tumor volume by 34%). In the future, the patient continued DLT LUE 5 MeV to the inguinal lymph nodes to SOD 40 Gy. The patient is still alive, for a year from the moment of relapse, without signs of further progression of the tumor process.

Example 3

A patient L.L.P., born in 1941, and \ b 4465, was admitted to the clinic in 2003 with a diagnosis of Colorectal cancer of the 1st stage, condition after surgical treatment in 2000. Relapse in the perineum, germination of the posterior wall of the vagina. Kolporragia. Anemia 2 tbsp.

On examination, the vagina is stenosed to the middle third with a small papillary tumor, which bleeds profusely upon contact.

The treatment was carried out according to the proposed method with a positive effect - the bleeding was stopped, partial tumor regression was achieved (2.4 fold reduction in volume). The patient is still alive for 8 months from the diagnosis of relapse, without signs of bleeding from the vagina, recto-vaginal fistula.

The proposed method helps to prolong life and improve its quality in a heavy group of patients who are practically not subject to antitumor treatment according to regulatory documents.

Claims (1)

A method of treating cancer patients with tumor lesions of the vagina, including chemoradiotherapy using cytostatics, remote and intracavitary irradiation, characterized in that during the first 3 or 6 days, only monochemotherapy is carried out, depending on the spread of the tumor lesion, while using a tissue application to introduce the cytostatic "Coletex" with proxifene and methyl sulfoxide added in a weight ratio of 4.5-5.0: 0.5-1.5, respectively, with a pre-additive wipe but moistened with a 20% solution of dimethyl sulfoxide and fixed with a tight tamponade of the vagina, wipes are changed every 24 hours, from 4 or 7 days at the same time as the application, they are contacted with high activity sources of ROD 2 Gy and remote radiation exposure after 4- 6 hours on the pelvis ROD 2Gy 10 sessions, 5 times a week.