Method of treatment of advanced breast cancer with tumor ulceration of the skin

 

(57) Abstract:

The method relates to medicine, more specifically to Oncology, and can find application in the treatment of locally advanced cancer, exacerbated by the collapse of the tumor. The method consists in carrying out detoxification, hemostatic, antibacterial and restorative therapy, after which the background prednisolone carry out joint chemoradiation treatment: chemotherapy using 5-fluorouracil in the form of napkins "Collex-5-ftur, and radiation therapy is performed in the mode average fractionation dose of 3 Grams daily to a total dose of 45 Gy to the base of the breast and up to 33-36 Gr zone of regional lymph flow, and after such treatment after 2-3 weeks hold traditional chemotherapy is one of the common schemes. The method allows to obtain a remission of up to 4.5 years, to increase the effectiveness of the treatment. 2 C.p. f-crystals.

The invention relates to medicine, more specifically to Oncology, and can find application in the treatment of advanced cancers, exacerbated by the collapse of the tumor.

The idea of locally advanced breast cancer (BC) in the literature a few blurry. However, most authors in this understood the organizational scheme of treatment of such patients includes neoadjuvant chemotherapy, local treatment (radiation, surgery and adjuvant therapy. To start the treatment of locally advanced breast cancer recommend with neoadjuvant (preoperative) chemotherapy.

Chemotherapy regimens use a variety of CMF (cyclophosphamide, methotrexate and 5-fluorouracil), scheme, including anthracyclines, taxanes, platinum drugs, and others. Also use combinations of these drugs with radiotherapy 2 Gy up to a total focal dose (SOD) 50 Gr.

There is a method of treatment of advanced breast cancer by regional chemotherapy [JVIR 1998, V9, N1, 91-96]. The method consists in the catheterization crtbegin access subclavian, internal mammary and breast arteries with subsequent perfusion chemotherapy (mitomycin, mitozantrone and methotrexate). The authors note that because the blood supply to the breast of the different patients is characterized by a large variability, not all of them manage to cover chemotherapy the tumor.

The feasibility of subsequent surgical treatment of locally advanced breast cancer currently widely discussed in the literature and expert opinions on this issue differ. Baillet F. et al. [Pisa Symposia in Oncology. Breast Cancer: From Biology to Therapy. Octo is terapii (vinblastine, the thiotepa, methotrexate, 5-fluorouracil and adriamycin) every 10 days over 2 months and radiation therapy (external radiation 23 Gy in 4 fractions plus interstitial therapy with 1921 20-30 Gy) and further chemotherapy within 12-18 months. The operation was used only in cases metroregions relapse was observed in 20% of patients. Moreover, 5 - and 10-year survival was 64% and 50%, respectively.

The possibility of organ-sparing surgery in locally advanced breast cancer in most modern publications is estimated very optimistic. The assumption is made of 2 main principles: 1) for early breast cancer with the size of the primary tumors up to 3 cm organ-sparing surgery in combination with radiation therapy is as effective as radical mastectomy; 2) patients with residual tumors up to 3 cm after neoadjuvant treatment can be performed the same local treatment, as with early breast cancer [New in cancer therapy. M., 1998, S. 37-38]. Contraindication to radical mastectomy is a direct extension of tumor to the chest wall muscle, lymph nodes of Rotter and the execution of palliative operations. After surgery all patients ledue is to be placed, surgery and radiation therapy and subsequent adjuvant chemotherapy can give high enough long-term results of treatment [Colozza M et. al. Am. J. Clin. Oncol. 1996, 19, 1, 10-17] with a median relapse-free survival, equal to 29 months. and with a median overall survival of 49 months. If, for example, [Massidda Century. et al. European J. Of Cancer. 1996, v. 3A, Suppl.2, pp8-14 (abstract)] holding neoadjuvant chemotherapy for breast cancer T4N1MO allowed to transfer 95% of patients (42) in operable condition, postoperative treatment, including radiotherapy and adjuvant chemotherapy, were not effective in preventing recurrence of the disease. 5-year overall survival was 38% and 32%, respectively.

Relative timing of radiotherapy in the treatment of locally advanced breast cancer, there is a wide range of opinions. The new trend is that radiation therapy after surgery and after adjuvant chemotherapy, although some spend it before, others after surgery, but before adjuvant chemotherapy, and the group of authors prefer the radiation therapy concurrent with adjuvant chemotherapy.

Thus, despite the apparent diversity of approaches to the treatment of the AI, local treatment (radiation and surgery) and adjuvant therapy.

A particularly difficult problem of treatment of breast cancer patients are common cancer with tumor ulceration of the skin. The frequency of this symptom varies widely and various data ulceration of the tumor nodules develop 18.6-50% of patients. This is usually accompanied by tissue necrosis with the inevitable infection and subsequent formation of malodorous bleeding tumor ulcers with abundant discharge, which greatly aggravates the clinical course of the disease. This, along with the local manifestations of neoplastic ulcers are the symptoms of intoxication due to absorption of the decay products and inflammation (fever, weakness, loss of appetite, malaise), as well as symptoms caused by anemia (weakness, decreased performance, paleness of skin and mucous membranes). In a laboratory study may reveal leukocytosis, shift leukocyte formula to the left, the EMAS. the decrease of level of haemoglobin and red blood cell counts.

Although the main method of treatment of disseminated breast cancer is the above-described therapy, severe clinical ka the investment antitumor treatment, because the healing process of ulcers in local toxicity caused by chemotherapy significantly prolonged. One of the first places in such cases extends symptomatic treatment, including the relief of the major symptoms of ulcers (inflammation, bleeding, unpleasant smell) and the prevention of their development. For this purpose, conduct antibacterial therapy through the selection of antibiotic sensitivity to it flora and detoxification, styptic and tonic therapy. And only if you reduce the signs of intoxication and discharge from the sores, you can start the active anticancer therapy. Otherwise, the continued growth of the tumor affects the blood supply, causing cell death, which are the perfect environment for microbial growth. Therefore, patients with neoplastic ulcers require constant local care: cleansing ulcers from necrotic masses and fungicidal treatment.

The choice of further and anticancer therapy depends on the stage of the disease, the General condition of the patient and the severity of neoplastic ulcers.

As a prototype we have used a method of treating a tumor expressing in BC, kwih ulcers, although mostly confined to the symptomatic treatment of such patients [Practical Oncology: breast cancer, N 2 (June) 2000, S. 54 - 56].

The technical task of the present invention was the development of effective and at the same time sparing treatment for advanced lung cancer, breast tumor manifestations of the skin.

This problem is solved by the fact that when carrying out non-specific drug and chemoradiation treatment of chemotherapy carried out through a 5-F-uracil, which is in the form of napkins stake-Tex-5-ftor" impose on the region of the tumor daily 2-3 times per day 4-5 days additional daily enter prednisolone 20-30 mg orally or 30 mg intramuscularly, radiation therapy is carried out on the background of the action of these drugs daily for 3 Gr per day to the total focal dose (SOD) 45 Gy at the base of the breast and to SOD 33-36 Gr zone of regional lymph flow, after radiotherapy, the dose of prednisolone every 2-3 days reduce by 5-10 mg, napkins "Collex-5-ftor" replace "Collex-CHG" or "stake-Tex with Dimexidum and use them to complete scarring, and 2-3 weeks after radiation therapy is carried out traditional chemotherapeutic treatment.

It is advisable as a traditional months, and as a non-specific treatment to use detoxification, hemostatic, antibacterial and restorative therapy.

Doing professionally for many years the treatment of cancer patients with different profiles, we have accumulated considerable experience in the treatment of common forms of cancer. However, the treatment of patients with acute epithelial and neoplastic ulcers, characterized by constant festering and bleeding, requiring daily treatment, anti-inflammatory and immunodeciency was no easy task.

Conducting non-specific drug treatment, including antibacterial, detoxification, styptic and tonic therapy, while maintaining the primary lesion does not provide a complete scarring of tumor ulceration of the skin, but contributes to the partial disappearance of the manifestations of ulcerative process (decrease of purulent discharge, stop bleeding, and so on ). However, note relieved clinical manifestations, you can go to anticancer therapy as primary treatment of breast cancer with tumor ulceration of the skin.

We drew unmanageability polymer-polysaccharide - sodium alginate, and various medications (furagin, metronidazole, propolis, chlorhexidine, Dimexidum, amiloretic, 5-fluorouracil, dimethylsulfoxide, and combinations of them in various combinations), distributed in the gel is biocompatible polymer capable of absorbing liquid [application for the invention "Multilayer medical material on a textile backing" N 98116005/14 from 21.08.98]. Given the need for constant discharge of secretions from the tumor ulcers, we decided to try to use napkins "Kreteks" in the treatment of patients with breast cancer, complicated by ulceration of the skin. Since the main type of treatment of such patients is, as said above, anticancer therapy, we were chosen for the study napkins "Collex-5-ftor" (5-fluorouracil).

Previously in the experiment on the animals (white mice, which was transplantability under the skin with the help of ascitic cells of Ehrlich carcinoma and sarcoma 37) we have studied the activity of several types of tissues (with 5-fluorouracil and its combination with other drugs) that bind these mice upon reaching the tumor with a diameter of 5-6 mm Antitumor activity of the tissues was estimated by the rate of tumor growth, as well as having survived ulitity experiments were subjected to statistical analysis by the method of student-Fisher. They showed rapid delivery of drugs to tumor lesion, a slight overall toxic effect and high chemotherapeutic effect.

Positive results of experimental studies has allowed us to conduct clinical research wipes "Collex-5-ftor" with the content of 5-fluorouracil on the surface wipes 3 mg/cm2when breast cancer with tumor ulceration of the skin.

5-Fluorouracil taken by us because it is the most studied and least toxic. And low toxicity appeared to be decisive in his choice, since patients with neoplastic ulcers high intoxication due to absorption of the decay products of the tumor and inflammatory process.

In Oncology practice 5-fluorouracil is used primarily for intravenous injection in a dose of 10-20 mg/kg daily for 3-5 days with an interval between courses of 4 weeks.

Use it topically in the form of wipes "Collex-5-ftor" in the treatment of advanced lung cancer, breast undertaken by us for the first time. Studies have shown, we were able to reduce the signs of intoxication and discharge from the ulcer, as well as tumor regression, and this result was reached us PR cm2a single dose of 5-fluorouracil is equal to 30 mg, and day - 60-90 mg (2-3-pay change these napkins per day), and the use of 5-fluorouracil in the form of wipes "Collex-5-ftor" virtually eliminates getting into the blood stream, reducing to a minimum the General toxic effect. At the same time, selective and prolonged accumulation in tissues provides long-lasting anti-tumor effect. The presence in tissues of sodium alginate with necrotic properties, promotes the regeneration of tissues of the breast.

Use in the treatment prednisolone allowed us to spend chemoradiation treatment without interruption, to prevent radiation, to reduce radiation reaction, to maintain a satisfactory General condition of patients (pressure, appetite and other functions of the body). Although because of the danger of the destruction of tissue and the possibility of bleeding in the presence of tumor ulceration purpose of prednisolone is contraindicated, in our opinion, due to the use of his background applications ulcers napkins "Collex-5-ftor" our patients we in any case have not observed a worsening of ulcerative process.

The combination of prednisolone and 5-fluorouracil provides the who, what, 5 times a week to SOD 45 Gr equivalent to the normal fractionation of 2 Gy, 5 times a week to SOD 60 Gy, and to SOD 33-36 Gr zone of regional lymph equivalent to SOD 44-48 Gr conventional fractionation. This enhances the antitumor effect, and for a shorter time. And long-term presence of the chemical in the exposure zone makes antitumor activity of combined treatment is optimal.

Replacement wipes "Collex-5-ftor" at the end of the proposed course chemoradiation treatment "Collex-CHG" or "Kreteks with Dimexidum" [the same patent] that have disinfectant and antiseptic action, allow to maintain therapeutic effect and to prevent recurrence of ulcers.

We observe in all cases, complete healing of the tumor ulceration was further allowed us to go to traditional chemotherapy in the form of a series of courses of chemotherapy, in particular the recommended 6 courses of CMF (cyclophosphamide, methotrexate and 5-fluorouracil). The implementation of such a treatment regimen, as has been shown in clinical trials of the proposed method, contributed to the extension and improvement of the quality of life of this category of patients.

SunOS is the IR cnerry 1.04.99, with a diagnosis of breast cancer T4cN2Mo with ulceration of the skin of the breast.

From the anamnesis: ill about 2 years old when first observed tumor mass in the left breast, which was gradually increased. A year later I went to the doctor to fill in sanatorium-resort card. It was recommended that after the sanatorium refer to an oncologist, but the patient prior to March 1999, i.e. in the course of the year, to the doctor did not address, while in the area of the tumor does not appear furunkuleze education with ulceration. District oncologist referred her for counseling in cnerry.

At admission he complained about the presence of tumor in the left breast with bleeding ulceration, General weakness, headache, nausea, pain in the left breast.

The results of the survey:

Locally: in the left breast can be seen on the upper quadrants of the tuberous tumor formation in the form of carbuncle with ulceration, bleeding and bad breath. Palpation - a tumor of about 10 cm in diameter, attached directly to the chest wall. In the left armpit deep in the dome is partially movable relative to surrounding tissues conglomerate enlarged lymph nodes, spas infiltration of the skin and destruction in the center (ulcer) with the presence of calcification and with the transition to the chest wall.

Almostentirely: foci of hyperfixation TS diameter of about 8 cm in the left breast and about 4 cm in the left armpit.

According to the results of ultrasound examination: moderately common fibroadenomatosis is a round spherical formation with hypoechoic contours of diameter 82 mm on the upper quadrants of the left breast.

Positron emission tomography (PET): a series of tomograms with 18F-deoxyglucose in the upper quadrants of the left breast is defined foci of increased isotope accumulation zone hyperfixation in the center with a diameter of 7.8 cm and a focus hyperfixation in the left axillary region with a diameter of 3.8 see

Histologically: on the background of red blood cells tumor cells of poorly differentiated adenocarcinoma.

Conclusion: breast cancer with the collapse of tumor metastasis in the axillary lymph nodes on the left.

From the first day of stay of the patient in the clinic she started treatment: daily intravenous aminocaproic acid (drip) in 100 ml N 5, on the same days gentamicin intramuscularly at 0.08 g, 2 times a day and vitamins B1 and B6 in turn 2 ml, then Cefazolin p the creators of dipyrone and 1 ml of 1% solution of demerol. Simultaneously conducted daily toilet sores with hydrogen peroxide and the imposition of a hemostatic sponge.

The patient's condition has improved, stopped bleeding ulcers, decreased pain.

With 9.04.99 on the area of the tumor every day 2-3 times a day began to take napkins "Collex-5-ftor". The ulcer gradually cleansed from necrotic masses, decreased redness of the skin around her, decreased pain.

With 14.04.99 on the region of the left breast with two tangential counter fields and shaped field in the region of the zones of regional lymph from the left started radiation therapy linear accelerator (LU-20-SL energy bremsstrahlung 6 MEV) using the average fractionation dose of 3 Gy per day, 5 times a week on the area of the tumor to a total dose (SOD) 45 Gy, equivalent to the normal fractionation of 2 Gy per day - SOD 60 Gy, and areas of regional lymph flow to the left (adodblite-axillary and parasternal area) 3 Gr and SOD 33-36 G, equivalent 44-48 Gr conventional fractionation. Radiation therapy in this mode was carried out on 04.05.99. All this time daily on the tumor continued to impose napkins "stake-Tex-5-ftor", removing them only for the session, the beam is on, and weekend 20-30 mg orally.

The patient's condition after a course of radiation satisfactory, tumor ulceration in the stage of scarring, emissions, virtually no.

With 05.05.99 napkins "Collex-5-ftor" was replaced by "Kreteks" with chlorhexidine, which is superimposed on the region of the tumor within 10 days, then used a napkin "Kreteks" with Dimexidum to complete cicatrization of the ulcer, which took about 2 months. May 5, prednisolone was administered daily oral 20 mg, 8 may - 10 mg, from 11 may to 5 mg per day, may 13, prednisolone was cancelled.

With 25.05.99 started polychemotherapy according to the scheme CMF, which was conducted during 4 weeks 1 week, respectively, may 25, June 1, June 8 and June 15. The CMF scheme included intravenous drip of 1 g of 5-fluorouracil and 40 mg of methotrexate and intramuscular 1 g of platinum. Chemoradiation treatment the patient would satisfactorily: the nausea was controlled by the intravenous injection of 5 mg of novabay in 10 ml of 0.9% sodium chloride solution; incurred 17.06.99 leukopenia was cropped three times (17.06, 18.06 and 19.06.99) subcutaneous injection of Neupogen 300 mg per injection.

29.06.99 patient was discharged from the clinic will satisfy the supervision of an oncologist at the place of residence with the recommendation to use napkins "Kreteks with Dimexidum" at the slightest suspicion on open sores and spend 6 to 8 weeks 2-week course of chemotherapy (due to a previously existing radiation) according to the same scheme CMF.

A second course CMF was conducted in the month of July: 9.08 and 16.08.99 was injected 40 mg methotrexate and 1 g of 5-fluorouracil and intramuscular injection of 1 g of platinum (under the control of the peripheral blood).

6.09.99 patient re-admitted to the clinic in cnerry. Her condition is satisfactory. On the site of ulceration of the breast formed stellate scar with palpable infiltration in the area of about 3, see the Regional lymph nodes were not determined, mammary gland soft, fresh infiltrates not.

On a mammogram (13.09) tumor site compared with mammography from 4.05.99 reduced in diameter up to 6 cm

With 14.09.99 started a course of chemotherapy according to the same scheme and in the same doses as in may-June, under the control of the peripheral blood. Emerged again (blood from 24.09) leukopenia was cropped 27.09 with Neupogen and chemotherapy was completed safely and on time. However 4.10.99 was marked pancytopenia, and therefore 4.10 and 6.10.99 continued introduction of Neupogen and an additional 30 mg of oral prednisolone during the week. To 14.10.99 leukopenia and pancytopenia have been cropped.

18.10.99 the patient was discharged from the hospital under observing. the status of its satisfactory at the place of the ulcer smooth stellate scar, infiltrative events no, axillary and infraclavicular lymph nodes was not determined, the right breast is not changed.

On the mammograms from 30.12.99 tumor site in the form of fibrous tissue decreased compared with the latest data mammography from 13.09.99 to 4.2 cm, in the right gland is normal.

Radiographs and CT scans of the lungs and mediastinum - without pathological changes.

Osteointegrated from 24.12.99 showed insignificant hyperfixation TS in the left hip joint. On radiographs of the right hip joint and lumbar-sacral spine pathological changes in the bones were not found.

Data ultrasonography of internal organs - without a pathology. Breast ultrasound: in the right breast moderately expressed phenomena of diffuse fibroadenomatosis, in the left - postradiation changes in the structure of nature. In the upper quadrants is determined by the inhomogeneous node size of 4 mm. Regional lymph nodes are not rendered.

Clinical analysis of a blood in norm.

With 10.01.2000, taking into account the possibility of the patient radiation and pancito the traveler has suffered its fair.

12.04.2000, patient newly admitted to the clinic in cnerry. Her condition is satisfactory. When clinical and radiographic examination (examination, mammography, breast ultrasound and abdominal cavity, radiography and tomography of the lungs and mediastinum, osteointegration, clinical and biochemical blood and urine) data for the presence of tumor recurrence in the breast and metastasis is not received.

5.05. and 12.05.2000) underwent a 2-week course of combination chemotherapy CMF scheme, which the patient felt fine.

20.09.2000, fifth hospitalization at the clinic. The patient's condition is satisfactory. The clinical-radiological survey data for continued tumor growth is not received. Held again 2-week course of chemotherapy (sixth course from start of treatment) CMF 4.10. and 11.10.2000, that the patient still has satisfactorily. Written under the supervision of the district oncologist.

11.11.2000, check (after 18 months from start of treatment) - no signs of relapse.

Thus, a patient with breast cancer with tumor ulceration of the skin and lymph node metastases is in a state of stable, remissi the breast cancer with bleeding ulcers, bringing patients physical and psychological suffering. All of them came fairly quickly zerubavel ulcers, relieve pain, reduce tumors and thereby improve their quality of life. The period of observation to date is from 1 year to 4.5 years. The two women after 2 years I developed distant metastases in the liver, one of them died from their disease progression, the rest are in remission and continue to occur.

The proposed method of treatment may become the method of choice in the treatment of this category of patients, for whom treatment is often denied, relating them to the category of hospice.

The method developed at the Central research x-ray radiological Institute and was clinically tested in 10 people with a positive result.

1. A method of treating breast cancer with tumor ulceration of the skin by non-specific drugs and chemo / radiotherapy, characterized in that the non-specific drug therapy is carried out for 7-10 days, chemotherapy spend by 5-fluorouracil, which is in the form of napkins "Collex-5-ftor" impose on the region of the tumor every day 2-3 times a day, after 4 to the Pius carried out on the background of the action of these drugs daily for 3 Gy per day to a total dose of 45 Gy to the base of the breast and up to 33-36 Gr zone of regional lymph flow, after radiotherapy, the dose of prednisolone every 2-3 days reduce by 5-10 mg, napkins "Collex-5-ftor" replace "Kreteks with chlorhexidine or Kreteks with Dimexidum and use them to complete scarring, and 2-3 weeks after radiotherapy chemo scheme F.

2. The method according to p. 1, characterized in that the non-specific drug therapy includes detoxification hemostatic, antibacterial and tonic.

3. The method according to PP.1 and 2, characterized in that they have 6 courses of cyclophosphamide, methotrexate and 5-fluorouracil, with the first three courses are conducted for 3-4 weeks every 6-8 weeks later for 2 weeks every 3 months.

 

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