Chemotherapy after bladder surgery. Intravesical chemotherapy and immunotherapy of superficial bladder cancer. Chemotherapy for bladder cancer, invasive forms

Krasny S.A., Sukonko O.G., Polyakov S.L., Zhukovets A.G., Rolevich A.I ()

INTRODUCTION

bladder cancer- one of the most common diseases encountered by oncourologists. Bladder tumors make up about 4% in the structure of oncological morbidity, and approximately 35% among oncological urological diseases. The incidence of bladder cancer is increasing. So, in 2002, the incidence of this pathology in the Republic of Belarus was 10.5 per 100,000 population (3.1% of the total number of cases), while in 1991 it was 7.7 per 100,000 (2.8%, respectively). ).

The most common histological type of bladder cancer is transitional cell. A distinctive feature of these tumors is that most of them (75-85% of all newly detected bladder tumors) are superficial, that is, in the Ta, T1 and Tis stages (carcinoma in situ, CIS). Ta - a tumor limited to the epithelium; T1 - Invading the lamina propria, but not the muscle layer of the bladder, carcinoma in situ - a flat (not papillary) intraepithelial tumor. Thus, in superficial bladder cancer, there is no invasion of the tumor into the muscular layer of the bladder. It has been shown that with such tumor spread, regional and distant metastases practically do not occur, and local effects are quite sufficient for the treatment of such tumors. In most cases, treatment for superficial bladder cancer begins with a transurethral resection (TUR). Depending on the characteristics of the patient group and the length of follow-up, up to 80% of superficial tumors recur and 2-50% progress to a muscle-invasive tumor. Intravesical therapy is currently widely used to prevent recurrence and, less commonly, treat superficial bladder cancer. There are two main types of intravesical therapy - chemotherapy and immunotherapy. These two types of treatment differ in their mechanisms of action, their effectiveness, the frequency of side effects and their severity. The most effective immunological drug in the treatment of superficial bladder cancer is the BCG vaccine. Despite the superiority of BCG over various chemotherapy drugs in preventing the recurrence of superficial bladder cancer, proven by numerous studies, it is believed that due to the risk of developing severe complications (BCG sepsis, infectious lesions of the lungs, liver, kidneys, prostate gland), BCG should be prescribed to patients with unfavorable prognosis for tumor recurrence and progression to muscle-invasive cancer. The rest of the patients after TUR of the bladder can undergo a course of intravesical instillations of various chemotherapy drugs.

INTRAVESICAL CHEMOTHERAPY

Intravesical chemotherapy has been under investigation since the 1960s. XX century. A large number of different studies have been conducted to determine the effectiveness of intravesical chemotherapy drugs in reducing the frequency of recurrence of superficial bladder cancer. Most of these studies had a relatively short follow-up (1-3 years). An analysis of the results of treatment of 5192 patients who participated in controlled trials of intravesical chemotherapy showed that under the influence of adjuvant treatment over a period of 1 to 3 years, the number of relapses was reduced by an average of 14%. ThioTEF, doxorubicin hydrochloride, mitomycin C, epirubicin hydrochloride, and etoglucid—the most commonly used drugs—reduce short-term relapse rates by an average of 17%, 16%, 12%, 12%, and 26%, respectively (Table 1). Controlled comparative studies of chemotherapeutic agents for intravesical use have generally failed to demonstrate any significant differences between individual agents.

Table 1.

In 2000-2001 a group of researchers from the United States led by M. Huncharek published 2 meta-analyses that analyzed 1-, 2- and 3-year disease-free survival in groups with and without adjuvant intravesical chemotherapy. Pooled data from 11 randomized controlled trials involving 3703 patients with newly diagnosed superficial bladder cancer showed a 30%-80% reduction in recurrence rates with adjuvant intravesical chemotherapy over 1-3 years compared with TUR alone.

Of all the chemotherapy drugs, mitomycin C proved to be the most effective. Long-term treatment protocols (i.e. 2 years) were more effective than short courses of instillations or single instillations.

Among patients treated for recurrent tumors, intravesical chemotherapy reduced the recurrence rate by 38% at the first year of follow-up compared with TUR alone, while at 2 and 3 years the recurrence rate decreased by 54% and 65%, respectively. Based on these data, it was concluded that intravesical chemotherapy has a significant effect on the recurrence-free period in patients with superficial bladder cancer.

The long-term results of intravesical chemotherapy were studied in a meta-analysis involving 2535 patients with stage Ta or T1 bladder cancer included in 6 randomized trials of intravesical chemotherapy of the third phase (median follow-up for the duration of the disease-free period was 4.6 years, time to the appearance of muscle invasion - 5.5 years and life expectancy - 7.8 years). As a result of the analysis of the obtained data, it was shown that, in general, adjuvant drug treatment (thioTEF, doxorubicin, epirubicin, intravesical mitomycin or oral pyridoxine hydrochloride) improves relapse-free survival, in particular 8-year, by 8.2% (44.9% versus 36.7%, p<0,01). Наряду с этим, не было выявлено существенной разницы между группами в длительности времени до прогрессирования (появления мышечной инвазии и отдаленных метастазов), а также продолжительности жизни. . Не наблюдалось существенных различий и в частоте возникновения вторых опухолей, что позволяет сделать вывод об отсутствии канцерогенных эффектов от проведенного лечения. Результаты приведены в таблице 2.

Table 2.

Indeed, while most studies show a benefit of chemotherapy in reducing the number of relapses during the first 2-3 years, there is little evidence of a long-term reduction in the number of relapses, and neither a decrease in the rate of disease progression nor mortality has been proven. When analyzing the results of treatment of 3899 patients with superficial transitional bladder cancer included in 22 randomized prospective controlled trials, D. Lamm et al. found that the disease progressed in 7.5% of patients treated with intravesical chemotherapy and in 6.9% of those treated with TUR alone.

While these results may cast doubt on the need for intravesical chemotherapy, chemotherapy is generally considered to play a role in the treatment of superficial bladder cancer. Intravesical chemotherapy has a clear benefit as it can reduce the number of relapses or at least increase the relapse-free period. Although intravesical chemotherapy is unable to influence disease progression, intravesical instillations of ThioTEF, mitomycin C, doxorubicin, or epirubicin are recommended in patients with well- and moderately differentiated tumors and stage Ta who have multiple tumors or a high recurrence rate at initial presentation. during the observation period.

Thus, there is a need to improve the effectiveness of intravesical chemotherapy. The main ways to improve this efficiency are the search for new chemotherapeutic agents, the combined use of chemotherapy and immunotherapy, the use of modifying effects, such as hyperthermia, and electrophoretic administration of chemotherapy drugs.

INTRAVESICAL ELECTROCHEMOTHERAPY

The use of electrophoresis - the electrokinetic movement of charged (ionic) molecules in an electric field - to enhance the transport of drugs into pathologically altered tissues has a long history in medicine. In contrast to passive drug diffusion, which depends on the concentration gradient, electrophoresis is much more efficient and, above all, depends on the strength of the current and the amount of electricity supplied. Positive ions of the drug are introduced into the tissue by the anode (positive electrode), negative - by the cathode (negative electrode). The transport of uncharged solutions is enhanced by two additional electrokinetic phenomena - electroosmosis - the transport of non-ionized molecules as hydration shells of ionized particles, and electroporation - increased tissue permeability under the influence of an electric field. To describe all these biophysical phenomena, the term "drug electrophoresis" was proposed.

Until recently, drug electrophoresis was primarily used to increase the penetration of drugs through the skin. Intracavitary electrophoresis can expand the possibilities of drug electrophoresis, increase local drug concentrations without systemic side effects in the treatment of a number of diseases. Since passive diffusion of intravesically administered substances into the bladder wall through the urothelium is negligible, enhancement of this process may make it possible to improve the results of drug therapy for bladder diseases.

In 1988, K. Thiel reported on intravesical electrophoresis of a positively charged drug proflavin, a chromosomal toxin, for the prevention of recurrence of superficial bladder cancer. This author described a specially designed intravesical anode and a circular external cathode. In the study of K. Thiel, out of 15 patients, no recurrence was observed in 40% of patients within 1 year. Local or systemic toxicity has not been identified.

There have been a number of experimental studies supporting the concept of increasing the transport of drugs through the urothelium to the deeper layers of the bladder wall (detrusor) by drug electrophoresis. So, S. Di Stasi et al. showed significantly increased transfer rates of mitomycin C and oxybutynin into the viable bladder wall by electrophoresis. Laboratory studies using human bladder preparations have demonstrated that drug electrophoresis increases the transport of mitomycin C through the urothelium 6-9 times compared to passive diffusion. It has also been shown in animals that carcinomatous areas of the urothelium are 100 times more permeable to water and electrolytes than the normal urothelium. It is very likely that carcinomatous areas have less electrical resistance than normal urothelium and thus there is some specificity for administering drugs to these areas.

In addition, several clinical studies have demonstrated that intravesical electrophoresis of local anesthetics leads to bladder anesthesia sufficient to perform various endoscopic procedures (transurethral resection of bladder tumors, bladder neck incision, bladder hydrodistension). Clinical and cystometric results of bethanechol drug electrophoresis (bethanechol) were significantly superior to those after bethanechol instillation without electrophoresis. Drug electrophoresis of lidocaine significantly reduced the pain associated with subsequent intravesical administration of capsaicin for the treatment of interstitial cystitis, and also virtually eliminated spastic bladder contractions compared to passive diffusion of lidocaine.

Data on systemic absorption of drugs and drug levels in the blood during electrophoresis are not enough. Two studies showed that blood levels of lidocaine after drug electrophoresis ranged from undetectable to approximately one-third of the therapeutic concentration. This suggests that minimal but clinically insignificant systemic drug administration can occur during drug electrophoresis.

Several studies have shown that mitomycin C drug electrophoresis can increase the efficacy of this cytotoxic drug in the treatment of superficial bladder cancer (Table 3). C. Riedl et al. performed 91 procedures on 22 patients with existing bladder tumors with a poor prognosis and achieved 56.6% complete regressions. Mitomycin C electrophoresis was well tolerated by patients, and the incidence of side effects was quite low (4.4% of patients had a moderate pain reaction during treatment, 14.3% had lower urinary tract symptoms within less than 24 hours after electrophoresis and 2.2 % of patients for more than 24 hours). None of these side effects required discontinuation of treatment.

In a study by M. Brausi et al. in the model of marker tumors, the effectiveness of electrochemotherapy with mitomycin (20 minutes) was approximately equal to the effectiveness of intravesical instillations of mitomycin (2 hours) (the frequency of complete regressions obtained in both groups was 40%). The relapse rate in responders was higher in the mitomycin instillation group (60%) than in the electrochemotherapy group (33%). Time to relapse was longer in the mitomycin electrochemotherapy group (mean 14.5 months versus 10 months). Due to the small number of patients, no definite conclusions can be drawn. However, the decrease in recurrence rate and longer relapse-free interval observed in the group of patients treated with electrochemotherapy can be explained by the greater penetration of mitomycin deep into the bladder wall under the influence of electric current. Since electrophoresis increases the transport of mitomycin by 6-9 times compared with passive diffusion, systemic side effects become possible. However, in this study, no significant systemic effects or changes in blood counts were observed in the two groups of patients.

R. Colombo et al. in their pilot study performed mitomycin C drug electrophoresis on 15 patients with superficial bladder cancer. The treatment regimen differed from the study by M. Brausi et al. the fact that 4 sessions of electrophoresis were performed instead of 8. In the electrochemotherapy group, 40% of complete regressions were noted compared to 27.8% in the treatment with mitomycin alone. Significant toxicity of therapy was not observed. Thus, the efficiency of mitomycin electrophoresis did not decrease with a decrease in the number of procedures, while the effect of mitomycin instillations decreased from 41.6% to 27.8% with 4 instillations compared to 8 in the study by M. Brausi et al. . This study also demonstrates the effectiveness of chemotherapy electrophoresis compared to conventional instillations. A small number of patients did not allow to show the reliability of differences in the effect of these treatments.

Table 3

Abbreviations: VPEF, intravesical electrophoresis; PR - complete regression; A - adjuvant therapy after TUR; M - marker tumors.

CONCLUSION

Thus, in a few studies, intravesical electrochemotherapy has shown a very encouraging effect. The lack of randomized controlled trials and the small number of observations do not allow any definite conclusion to be drawn. However, preliminary data suggest the potential effectiveness of this approach and the need for further research into electrochemotherapy for bladder cancer.

LITERATURE

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To improve the results obtained during therapeutic measures aimed at eliminating superficial bladder cancer in men, adjuvant and intravesical chemotherapy is used in most cases, thanks to which, by achieving maximum local effectiveness, it is possible to prevent the development of most side effects from ongoing systemic therapy. The main task in TUR (transurethral resection) is to prevent the transplantation of pathogenic cells, and after radical TUR - to prevent progression.

Indications

Among the main indications for which it is necessary to perform chemotherapeutic procedures, the following are distinguished:

• diagnosing cancer in situ;
• multiple neoplasms, affecting the bladder, when the possibility of transurethral resection is excluded and there are certain contraindications to cystectomy.

In addition, chemotherapy should be used in case of poorly performed previous surgical intervention.

Contraindications

The formation of relative contraindications to the procedure is based on some factors:

• prevalence malignant tumors;
• metastasis;
• dimensions tumor neoplasm of the affected organ.

Chemotherapy is not carried out with:

• diseases mental character;
• cachexia;
• cystitis;
• pregnancy;
• individual intolerance to the components that make up the drug;
• strong hematuria;
• intoxication, flowing in a severe form;
• inflammatory processes;
• dissemination metastases outside the bladder;
• insignificant containers cavities (less than 150 milliliters);
• tuberculosis and other serious pathological conditions.

It is also important to take into account the general condition of the patient.

Used drugs

The rapid development of the use of chemotherapeutic drugs in the treatment of malignant tumors of the bladder was noted in the 80s of the last century. This fact is explained by the fact that the effectiveness of these drugs has been scientifically proven, thanks to numerous studies.

The most requested tools include:

• Mitomycin C;
• Vinblastine;
• doxorubicin;
• Cisplatin;
• Ifosfamide;
• 5-fluorouracil;
• Carboplatin;
• Cyclofosvan.

It was these drugs that were used in the development of schemes for conducting chemotherapeutic measures.

In addition to the traditional configurations of polychemotherapy, researchers have begun to treat more modern anticancer drugs with increased attention:

• gemcitabine;
• Paclitaxel;
• Docetaxel.

The properties of both a single drug and their combinations have been actively studied.

The scheme of using drugs depended in many ways on the degree of the course of the cancer process.

So, in the treatment of stage 1 cancer, if the patient had a high risk of recurrence, then after transurethral resection it was recommended to receive Mitomycin C or intravesical BCG.

At the second and third stages, neoadjuvant chemotherapy is recommended, during which platinum-containing regimens (gemcitabine + cisplatin) were used before cystectomy, if kidney function was preserved, and the general condition of the patient was at a satisfactory level.

When carrying out chemotherapeutic measures at the fourth stage of cancer, platinum-containing combination chemotherapy with the same drugs that are used in the previous treatment option is considered standard. At stage T 4b, radiation therapy is also allowed.

If cisplastin is contraindicated for a patient, carboplatin combination or monotherapy with taxanes or cytabin is prescribed.

Side effects

The likelihood of adverse reactions, as well as their severity, will depend on several factors, which include:

• the drug used;
• dosage;
• individual intolerance to the components.

Each chemotherapeutic agent has its own negative effects, which will be discussed in more detail by the attending physician. List of the most common adverse reactions to bladder tumor chemotherapy:

• increased fatigue and pronounced weakness;
• nausea and vomit;
• bleeding;
• decrease in concentration blood Taurus;
• absence appetite
• rapid loss weight;
• brittleness nails;
• dropping out hair;
• feeling dryness in the mouth;
• formation ulcers on the mucous membranes of the oral cavity, rectum and bladder;
• infertility.

When conducting intraphysical chemotherapy, side effects are less common and somewhat less in contrast to systemic treatment. This is due to the effect of chemotherapy drugs directly on the mucous membrane of the affected organ and only a slight penetration into the composition of the blood fluid.

One of the most common side effects in this case is irritation of the skin of the perineum and bladder. This pathological reaction is accompanied by symptoms characteristic of the development of cystitis. The patient notes discomfort when going to the toilet, frequent urge to remove urine. In one patient and ten, rashes may appear on the skin of the upper and lower extremities.

Efficiency

Based on all the drugs used in the treatment of a malignant tumor of the bladder, certain chemotherapy regimens have been developed. Studies have shown that due to the combination of these funds, more than half of the patients managed to achieve positive dynamics.

It has been proven that it was possible to obtain maximum effectiveness in advanced cancer with the combination of M-VAC (Cisplatin + Methotrexate + Doxorubicin + Vinblastine).

Data were also published on the effect obtained as a result of the use of two chemotherapeutic regimens - M-VAC and CisCA (Doxorubicin, Cisplastin and Cyclophosphamide). Thus, the following conclusions were drawn:

• partial and complete regression was achieved in 65 and 49 percent of cases;
• average life expectancy was 11.2 and 8.4 percent, respectively.

Thus, once again it was possible to prove that the combination of M-VAC is the most effective in relation to other chemotherapeutic regimens.

In addition to the fact that traditional chemotherapy regimens were widely used, scientists were also interested in more modern drugs, which include Docetaxel, Paclitaxel and Gemcitabine. They began to be actively studied both separately and in joint application.

Gemcitabine was one of the first to be proven effective in locally advanced and disseminated bladder cancer. A similar reaction was found during the first phase of treatment. As a result, a positive result was recorded in four out of fifteen patients. The duration of the effect averaged 16-32 weeks. Subsequently, these results were confirmed in the course of several more studies.

So, in the monotherapy regimen, gemcitabine showed its effectiveness in 26.6%, in other words, in every 4th patient, which is a high indicator.

The combination of cisplatin and gemcitabine has been extensively studied in disseminated malignant tumors. Patients received these drugs as the first line, while they received a dose of Cisplatin only once every 7 days. In a study of the Canadian group, a positive effect was achieved in 71 percent of cases. Thus, it was possible to obtain a two-fold increase in the rate of complete response to this regimen (20%), despite the fact that this indicator is 10% with Gemcitabine monotherapy.

In addition, it has been proven that the combination of gemcitabine with cisplatin contributes to a significant improvement in the quality of life of patients, in contrast to the M-VAC regimen.

Thanks to the results of chemotherapy treatment of bladder cancer achieved in recent decades, it became possible not only to improve the quality of life of the patient, but also to increase its duration. It can be stated with certainty that a new modern standard of chemotherapy has appeared - the regimen of gemcitabine and cisplatin.

In intravesical therapy for bladder cancer, drugs are injected directly into the bladder through a catheter, instead of being given intravenously or taken in tablet form. Immunotherapy and chemotherapy can be carried out by the method.

intravesical chemotherapy. Single intravesical instillation of chemotherapy after TUR.

If the superficial tumor can be completely and safely removed during TUR without signs of deep invasive growth, a single instillation may be given postoperatively. If you have multiple tumors, a single instillation is not indicated, if the surgical procedure affects the deep layers of the bladder wall, there is a risk of bladder perforation, or postoperative bleeding is too heavy.

A single instillation immediately after surgery destroys tumor cells floating in the post-TUR fluid and kills residual tumor cells at the site of removal. This reduces the risk of relapse. It is recommended to carry out instillations as early as possible, usually within a few hours after TUR.

The drugs are injected directly into the bladder through a catheter that is inserted during or after the TUR. The main side effects of intravesical instillation are irritation and burning sensation in the bladder, which disappear after a few days.

Additional intravesical chemotherapy after TUR.

Additional intravesical chemotherapy after surgery depends on the risk group. If you have a low risk of recurrence and progression, then a single instillation after TUR is sufficient to reduce the risk of recurrence and is considered standard treatment. If you have an intermediate-risk tumor, then a single instillation may not be enough, so additional chemotherapy injections may be required. The optimal number and frequency of instillations have not been determined.

Intravesical immunotherapy BCG (Bacillus Calmette - Guerin)

Bacillus Calmette-Guérin (BCG) is a strain of attenuated live bovine tuberculosis bacillus. For this reason, it is very important to tell the doctor about any history of tuberculosis, even if it was only a suspicion. You must report any immunotherapy you have had in the past.

BCG activates the immune system by causing superficial inflammation in the bladder, which attracts and stimulates immune cells to destroy cancer cells. Treatment usually begins a few weeks after TURP and is given once a week for 6 weeks. Long-term "maintenance" therapy of BCG is sometimes carried out by extending therapy up to 12-36 months. Studies have shown that BCG therapy reduces the risk of progression of all types of non-muscle invasive tumors.

BCG toxicity

BCG treatment is known to have more side effects than intravesical chemotherapy. BCG can cause a burning sensation in the bladder and flu-like symptoms such as fever, chills, and fatigue. Rarely, BCG enters the circulatory system and spreads to other organs leading to a generalized infection (sepsis). In this case, a severe fever may appear, which does not decrease when taking medications. In such a situation, you should contact your doctor, who will prescribe antibiotics used to treat tuberculosis for several weeks.

Treatment of Side Effects of Immunotherapy and Chemotherapy

Side effects may be general, common, or unusual. You must tell your doctor if you have any of the symptoms that you have. Try to describe your symptoms as accurately as possible. Notice how often they recur and how they affect your daily life. In some cases, a temporary interruption of treatment, a change in dose, or a complete cessation of treatment may be considered.

Common Side Effects

Some common side effects include fatigue, nausea, diarrhea, high blood pressure, and changes in taste.

You may experience fatigue, i.e. feel more tired than usual, feel weak, decrease concentration, and after sleep you do not feel better.

If you are experiencing fatigue, some methods may help:

• Write down the things that make you feel energized and prioritize them throughout the day or week.
• Ask for help with household chores
• A short sleep of 1-1.5 hours is needed several times during the day.
• Try to be as active as you can. A short walk every day is better than a long walk once a week.

During treatment, you may experience nausea and vomiting. You will be given symptomatic treatment. May also help:

• Eating smaller amounts of food, but drinking plenty of fluids throughout the day.
• Eat more cold foods than hot ones. Hotter causes nausea more often.

Another common side effect of treatment is diarrhea, which can lead to dehydration. Important:

• Drink more than usual.
• Avoid foods that you think make diarrhea worse.
• Follow the rules of personal hygiene
• See your doctor for symptomatic treatment

Blood pressure may also rise, especially at the beginning of treatment. This is normal with this type of therapy. Blood pressure can be controlled with medication prescribed by your doctor. If you feel dizzy or have a headache, tell your doctor.

Chemotherapy can cause a change in taste sensations. Perhaps there will be an aversion to the foods you are used to. The best way to find out what kind of food you like is to try different things:

• Drink water before meals to neutralize taste buds.
• If red meat seems weird, try white meat or fish, or vice versa.
• If hot food seems weird, try eating it cold or vice versa.
• Try using more or less spices
• Use a plastic fork and knife if it tastes like metal

In the structure of oncological pathology, bladder tumors make up about 4%, and among oncological urological diseases - about 40%. In recent years, there has been an increase in the incidence of bladder cancer. Thus, in 1998 in the Republic of Belarus this indicator reached 10.8 per 100 thousand people, while in 1991 it was 7.7 per 100 thousand people.

Transitional cell carcinoma of the bladder (TCCC) is the most typical histological type of cancer of this localization. It should be noted that 75-85% of all newly diagnosed bladder tumors are superficial, i.e. stage T a, T1 and Tis (carcinoma in situ, CIS) . Ta - a tumor limited to the epithelium; T1 - tumor that invades the basement membrane, but not the muscle layer of the bladder; Tis carcinoma is a flat (not papillary) intraepithelial tumor. Thus, in case of superficial bladder cancer, there is no invasion of the muscle layer by the tumor, regional and distant metastases practically do not occur, and local effects are quite sufficient for the treatment of such tumors. In most cases, the initial treatment for superficial SCBC is transurethral resection (TUR) of the bladder. Depending on the characteristics of the patients and the duration of follow-up, up to 80% of superficial tumors recur after TUR, 2-50% progress to a muscle-invasive tumor. Intravesical therapy is widely used to prevent recurrence and treat superficial bladder cancer. However, at present there is no consensus on specific indications for this therapy, the optimal drug has not been chosen, and there are conflicting views on the need for maintenance therapy.

To address the issue of the need to prescribe adjuvant intravesical therapy, the degree of malignancy of the tumor is of primary importance. Regardless of stage, grade 3 tumors recur in 70% of cases, and the risk of progression within 3 years is 45%. For tumors T 1G3, the progression rate reaches 52%, and the mean time to progression is 12.7 years. During the first 5 years, tumor progression to invasive is noted in 35% of patients, in 16% - within 5 to 10 years after diagnosis, and in 12% - from 10 to 15 years. 25% of patients die from cancer within the first 5 years and another 10% within 5-15 years. Such an unfavorable prognosis necessitates intravesical therapy in patients with low-grade SCBC, regardless of the stage of the tumor.

Carcinoma in situ(CIS) is known to be a highly aggressive tumor with a high potential for invasive growth and metastasis. When concomitant CIS is detected, there is a high risk of disease progression. For example, in the presence of a tumor T 1G3 The presence of CIS significantly increases the risk of disease progression (65% over 5 years). Therefore, the detection of even a small focus of CIS in the bladder is considered an indication for intravesical therapy.

Stage T and low-grade tumors progress in 7% of patients within 7 years, they can be treated with transurethral resection alone if no other risk factors for progression are present. However, multiple Ta tumors are a relative indication for intravesical therapy. Low-grade Ta tumor recurrences can only be treated with repeat TURBT, but if recurrences occur within the first 2 years after TURBT, intravesical therapy should be considered. In stage T1, tumor cells have access to blood and lymph vessels in the submucosal layer of the bladder. In this case, the progression rate reaches 30% or more, which necessitates intravesical therapy (Table 1, see the paper version of the journal) .

Adjuvant intravesical therapy is also indicated in cases of positive urinalysis shortly after TUR (indicating residual tumor in the bladder), frequent tumor recurrence, and concomitant urothelial dysplasia.

In a pool of data from 21 studies involving 3404 patients, only 49% of patients did not relapse after a single TUR. It is concluded that intravesical therapy should be used only in patients with a high risk of recurrence or progression of the disease.

In other words, intravesical therapy should be given to those patients who, based on tumor characteristics, have a higher risk of recurrence after TUR (Table 2, see paper version of the journal). For high-risk patients, the goal of treatment is to prevent tumor progression, thereby avoiding cystectomy and reducing the risk of death from SCBC. When intravesical therapy is used in patients at low risk, the goal of treatment is to reduce the rate of tumor recurrence, thereby improving patients' quality of life and reducing healthcare costs for treatment of recurrent tumors.

It is necessary to dwell on two main types of intravesical therapy with different mechanisms of action, indications, time of administration and effectiveness - intravesical chemotherapy and immunotherapy.

Intravesical chemotherapy

As mentioned above, if the tumor belongs to the group with an unfavorable prognosis, then it is advisable to use intravesical therapy after TUR to prevent recurrence and progression of the tumor into a muscle-invasive one. When using intravesical chemotherapy, the first goal is quite achievable, while the second is doubtful.

Why do superficial bladder tumors recur? H. Akaza et al. suggest that there are four causes of recurrence, which are not mutually exclusive: 1) implantation ("scattering") of tumor cells in the epithelium of the bladder during transurethral resection; 2) growth of accompanying microscopic tumors; 3) non-radical TUR; 4) the appearance of new (“second primary”) tumors of the bladder.

An analysis of the results of treatment of 3614 patients who participated in controlled trials of intravesical chemotherapy showed that within 3 years the number of relapses was reduced by an average of 14% compared with surgical treatment. ThioTEF, doxorubicin hydrochloride, mitomycin C, epirubicin hydrochloride, and etoglucid, the most commonly used drugs, reduced short-term recurrence rates by 17%, 16%, 12%, 12%, and 26%, respectively. Controlled comparative studies of various chemotherapy drugs have generally failed to demonstrate any significant differences in their effectiveness.

ThioTEF. This alkylating drug is the only intravesical chemotherapy agent approved by the FDA for the treatment of papillary SCBC in the United States. Its use reduces the risk of tumor recurrence by an average of 16% (-5-41%). The results of ThioTEF therapy are comparable to newer and more expensive chemotherapeutic agents if 367 patients from the Medical Research Council (MRC) study who received the drug at low concentrations were excluded from the pooled analysis.

Mitomycin C. Controlled studies have shown no advantage for the most expensive of the chemotherapeutic agents, mitomycin C, over other intravesical chemotherapeutic agents. For tumors T a / T1, the complete regression rate with mitomycin C is about 36%, and the relapse rate is reduced by an average of 12% (1-42%). A single instillation of mitomycin C immediately after TUR significantly reduces the rate of early tumor recurrence in superficial bladder cancer with a low risk of recurrence, but this effect decreases over time. Maintenance therapy does not improve treatment outcomes, and long courses are not superior to short courses of chemotherapy.

Doxorubicin- anthracycline antibiotic with a wide antitumor spectrum of action. The number of relapses in its application is reduced by an average of 16%. Doses of 30 to 90 mg at 1 mg/mL have been used without significant difference in efficacy. The best results are observed when using a single early postoperative instillation of the drug, maintenance therapy does not improve them. A. Kamat et al. Oral quinolone antibiotics have been found to produce a synergistic effect when combined with intravesical doxorubicin.

Epirubicin. The epimer of doxorubicin - epirubicin in the form of a single intravesical instillation immediately after resection is able to reduce the incidence of relapses of SCBC by an average of 26% (60% with TUR alone and 34% with adjuvant treatment with epirubicin). As with other studies on the use of chemotherapeutic agents such as doxorubicin and ThioTEF, epirubicin maintenance was not shown to have additional efficacy.

Etoglucid - an alkylating agent. K. Kurth et al. when comparing the effectiveness of etoglucid and doxorubicin in a randomized trial, etoglucid was found to be more effective when administered intravesically than doxorubicin or TUR alone. Compared with the control group, etoglucid reduced the recurrence rate by 31%, doxorubicin only by 13%.

Long-term results of intravesical chemotherapy. In a meta-analysis of 2535 patients with SCBC stage T a or T1 included in 6 randomized trials of phase III intravesical chemotherapy (follow-up averaged 7.7 years), there was a statistically significant (P<0,01) снижение частоты рецидивов у 1629 пациентов, получавших тиоТЭФ, доксорубицин, эпирубицин, митомицин внутрипузырно или пиридоксина гидрохлорид внутрь, по сравнению с 906 пациентами, пролеченными только ТУР мочевого пузыря . Эти результаты демонстрируют долговременное снижение риска рецидива опухоли в среднем на 7%. Адъювантное лечение не влияло на частоту прогрессирования, сроки до появления отдаленных метастазов и выживаемость.

Indeed, while most studies demonstrate the benefit of chemotherapy in reducing relapse rates over the first 2–3 years, there is little evidence of long-term reduction in relapse rates and no evidence of reduction in disease progression and mortality. In an analysis of the treatment outcomes of 3899 patients with superficial CRCM included in 22 randomized prospective controlled trials, D. Lamm et al. found that the disease progressed in 7.5% of patients treated with intravesical chemotherapy and in 6.9% after TUR.

H. Akaza et al. hypothesized to explain these observations. The authors believe that intravesical chemotherapy is effective against the dissemination of tumor cells during TUR of the primary tumor, as well as against residual microscopic foci of cancer or residual tumor after non-radical TUR, but does not prevent the subsequent emergence of new "primary" tumors, which, apparently, lead to to progression. This theory seems very plausible and emphasizes the need to find ways to prevent the progression of the disease that causes death from superficial bladder cancer. The assumption of H. Akaza et al. that intravesical therapy is ineffective against "second primary" tumors is based on data reflecting the frequency of relapses at various times after TUR. While intravesical chemotherapy reduces the risk of recurrence during the first 3–6 months after TUR, as the time after resection increases, the difference in recurrence rate becomes less significant. The authors explain this by saying that intravesical chemotherapy may affect recurrence due to implantation of cells or microscopic tumors, but not the risk of "relapse" due to the appearance of a new tumor. Such tumors are diagnosed in more remote terms after a resection.

Although intravesical chemotherapy does not affect disease progression, instillations of ThioTEF, mitomycin C, doxorubicin, or epirubicin are recommended in patients with well- and moderately differentiated tumors and low stage (T a, grade 1-2) who present with multiple tumors at initial presentation or have a high recurrence rate during follow-up. Intravesical chemotherapy would be of obvious benefit to such patients, as it could reduce the number of relapses, or at least increase the time to relapse.

There is interest in the use of immediate adjuvant postoperative intravesical chemotherapy. This method of treatment is based on the first mechanism of recurrence, namely the implantation, or "scattering", of tumor cells during resection. The fact is that after TUR in the bladder, areas without epithelial lining appear, as a result of which the underlying tissues come into contact with the contents in the lumen of the bladder. The presence of such sites and the desquamation of a large number of tumor cells during TUR may lead to implantation of tumor cells in the resection wound.

One of the most significant studies of immediate postoperative chemotherapy was a prospective randomized trial by H. Zincke et al. who compared immediate adjuvant administration of ThioTEF (60 mg), doxorubicin (50 mg) and saline. Relapses were observed in only 30% of patients treated with ThioTEF, in 32% of those treated with doxorubicin, and in 71% of patients in the control group. It follows that the 40% reduction in recurrence rate is due to the prevention of tumor cell implantation. However, this seems highly unlikely. And it is quite incredible that after a single dose of ThioTEF, a microscopic or residual tumor can be cured. However, similar results have been obtained in other clinical studies. For example, the European Organization for Research and Treatment of Cancer (EORTC) conducted a study in 431 patients comparing a single dose of epirubicin (80 mg) with water in a control group. The study demonstrated a significant benefit of immediate administration of epirubicin in reducing the incidence of tumor recurrence. A review by P. Schellhammer raises the issue of combining immediate intravesical chemotherapy with an induction course of BCG immunotherapy 1–2 weeks after TUR followed by BCG maintenance. It is assumed that such combined chemoimmunotherapy can significantly reduce the incidence of both recurrence and tumor progression.

Intravesical immunotherapy

Immunotherapy for superficial bladder cancer became widespread after A. Morales et al. in 1976. published data on the effective intravesical use of the BCG vaccine. Subsequent studies have shown that intravesical BCG immunotherapy can reduce the recurrence rate and prevent the progression of SCCM. It is considered to be the most effective intravesical treatment for superficial bladder cancer. BCG therapy is significantly superior to chemotherapy in reducing the rate of disease progression. Controlled comparative studies have demonstrated the superiority of BCG over the administration of thioTEF, doxorubicin, and mitomycin C. BCG immunotherapy reduces the recurrence rate by an average of 40% compared to 14% with chemotherapy.

In a controlled prospective study involving 94 patients, M. Melekos et al. demonstrated a reduction in relapse rate from 59% in the control group to 32% in the BCG treatment group. S. Krege et al. found recurrence in 56 (46%) of 122 patients treated with TUR alone compared with 26 (25%) of 102 patients who received intravesical BCG once a week for 6 weeks and then once a month for 4 months after TUR.

H. Herr et al., evaluating the results of treatment of 86 patients, found that the time to progression to a muscle-invasive tumor in the treatment of BCG increased significantly. In this study, progression occurred in 35% of cases in the control group compared to 28% in the BCG group. In addition, with the use of BCG, mortality decreased from 37% to 12% (P< 0,01). Цистэктомия потребовалась 42% пациентов в контрольной группе и только 26% пациентов, пролеченных БЦЖ. У больных в группе БЦЖ среднее время до цистэктомии увеличилось с 8 до 24 мес .

Long-term follow-up studies have shown an average 40% reduction in tumor recurrence (from 60% to 20%), and a mean reduction in tumor recurrence with BCG from 28% to 14%. The Southwestern Cancer Group (SWOG) found that for patients with superficial tumors without comorbid CIS, the five-year relapse-free survival after doxorubicin treatment is 17% compared with 37% after BCG therapy (P = 0.015).

A double-blind controlled study by D. Lamm showed that the use of 40,000 IU of vitamin A, 100 mg of vitamin B 6, 2.0 g of vitamin C and 400 IU of vitamin E can further reduce the number of relapses by 40% in patients receiving BCG.

U. Nseyo and D. Lamm summarized the results of 6 clinical studies comparing TUR and TUR alone with subsequent intravesical BCG immunotherapy and found a significant benefit of BCG therapy in 5 of 6 studies. One study that found no superiority of BCG included only 77 patients, and the control group had a relatively low recurrence rate of 42%.

BCG immunotherapy is highly effective in the treatment of CIS. In several studies involving more than 1500 patients, the rate of complete regressions of CIS with BCG treatment averaged 70%. For comparison: the frequency of complete regressions during chemotherapy is on average 38-50% for thioTEF, 48% for doxorubicin and 53% for mitomycin C. On average, less than 20% of patients who receive chemotherapy live without a relapse in the long term. In the SWOG study, patients with CIS had a 34% chance of complete regression with doxorubicin and 70% with BCG (P< 001) . Безрецидивная выживаемость в течение 5 лет составила 18% для доксорубицина и 45% для БЦЖ. В настоящее время БЦЖ считается препаратом выбора для лечения СIS, поскольку может повышать выживаемость больных и позволяет в ряде случаев избежать цистэктомии.

H. Akaza et al. 157 patients with superficial bladder cancer shared their experience with BCG treatment. Complete regression rates reached 84.4% and 66.4% for 32 patients with CIS and 125 patients with T tumors. a/T1, respectively. It is assumed that optimization of the BCG vaccine regimen can increase the frequency of complete regressions to 87% and provide a long relapse-free period in 83% of patients. There is also evidence that the efficacy of a single 6-week course of BCG can be significantly improved with BCG maintenance (from 86% to 92%, P<0,04) . Следует помнить, что CIS - высокоагрессивный мультифокальный рак. Неэффективность 6-недельного курса БЦЖ должна рассматриваться как сигнал, предупреждающий о том, что больному требуется немедленное обследование для исключения мышечной инвазии или CIS уретры и верхних мочевых путей .

BCG is used to treat residual unresectable bladder cancer with 35 to 84% success rate. However, BCG therapy should not be considered as an alternative to surgical removal of a resectable tumor. For the treatment of muscle-invasive cancer, intravesical administration of BCG as monotherapy is not recommended. In a report of 13 patients with SCCM in stage T 2 or more treated with BCG, only one patient had neither local recurrence nor metastases, 10 developed disseminated disease, 7 patients died of metastases.

Thus, the indication for intravesical BCG therapy is CIS or T tumors. 1 and/or G3 that have been completely or incompletely resected. BCG treatment is recommended for those patients who have failed intravesical chemotherapy for low-stage, well-differentiated tumors. Unlike chemotherapeutic agents, BCG should not be administered immediately after tumor resection due to the potential for severe systemic infection.

The optimal dose of BCG has not been clearly established, but there are currently recommendations for two commercially available drugs, TheraCys-Connaught and TICE-ORGANON. Today, the intravesical use of the BCG vaccine "Imuron" has become available. It is currently believed that at least 10 million living organisms are required for intravesical BCG therapy to be effective. Treatment with BCG usually begins 2 weeks after TUR. After instillation, patients should keep the injected liquid for approximately 2 hours. To facilitate contact of the drug with the entire surface of the bladder, the patient is recommended to change the position of the body at regular intervals. Excessive use of lubricants to lubricate the catheter during instillation can lead to a clinically significant decrease in the number of viable mycobacteria injected and poor contact of BCG with the bladder mucosa. Therefore, the use of catheters that do not require lubrication is of interest.

Supportive care

One of the important ways to increase the effectiveness of intravesical BCG treatment is maintenance therapy. J. Witjes et al. published the results of their study of 104 patients with recurrent superficial SCCC with a poor prognosis, in which patients received a 6-week course of intravesical BCG instillations followed by follow-up, including urinalysis, cystoscopy, and bladder biopsy every 3 months. Of the 65 patients with an ineffective initial course of treatment, 57 were prescribed an additional 6-week course of therapy. One 6-week course of BCG was successful in 36% of patients treated prophylactically, in 37% of patients with CIS, and in 41% of patients treated for residual tumor. Efficiency for the entire population of patients who received one 6-week course of BCG was 37.5%. A second 6-week course of BCG was successful in 65% of patients treated prophylactically, in 71% of patients with CIS, and in 40% of patients treated for residual tumor. The effectiveness of BCG for all 57 patients who received the second course was 59.6%. Of the 6 patients who refused the second 6-week course of BCG, 4 relapsed, and 3 of them had invasion into the muscular layer of the bladder.

W. Catalona et al. reported that 44% of 100 patients with superficial SCBC had complete regression after one 6-week course of BCG, while the total number of complete regressions increased to 63% after a second 6-week course of BCG. Thus, a single induction 6-week course of BCG in some cases does not provide optimal therapy for superficial bladder cancer.

Although two 6-week courses of BCG are better than one, the 6+6 regimen is not as effective as the 6+3 regimen proposed by D. Lamm in the SWOG study. In patients who received a 6-week induction course of BCG followed by three weekly instillations of BCG after 3, 6 months and then every 6 months for 3 years, the relapse rate was significantly lower and the relapse-free period was longer than in patients who received only the induction course . After only one three-week maintenance course of BCG instillations, 87% of patients with CIS had complete regression, 83% of patients with CIS or rapidly recurring T tumors. a/T1 SCCM were without recurrence.

During BCG therapy, a number of immunological changes are observed, such as infiltration of the bladder walls with mononuclear leukocytes (CD4+ and CD8+ lymphocytes, macrophages, B-lymphocytes) and an increase in the concentration of various cytokines in the urine (interleukin-1, -2, -6, -8, -10, tumor necrosis factor and interferon-γ). The study of the dependence of the effectiveness of BCG therapy on the level of cytokines in the urine showed a high prognostic significance of the latter. Thus, J. Fleischmann et al. revealed the prognostic value of the level of interleukin-2 and/or inhibitor of interleukin-2 in the urine; F. Saint et al. demonstrated the predictive value of urinary interleukin-2 levels for tumor recurrence.

Urinary cytokine levels peak in most patients after the sixth BCG instillation, but in patients with prior induction therapy, cytokine levels peak after 3 weeks. A long course of weekly BCG instillations can suppress the immune response and greatly increase the toxicity of the treatment. Unlike chemotherapy, in which an increase in dose leads to an increase in cytotoxicity, the dose-response curve for BCG is bell-shaped. An overdose of BCG can reduce the antitumor effect and even stimulate tumor growth.

When discussing the best regimen for administering BCG, the toxicity of this treatment must be taken into account. In the SWOG study, toxic effects requiring discontinuation, dose reduction, or isoniazid administration occurred in 26% of patients receiving maintenance therapy compared with 9% of patients receiving induction BCG alone (R< 0,0001) .

Thus, it seems rational to single out a subgroup of patients for whom the appointment of maintenance BCG therapy is especially indicated. In patients with a good prognosis for cancer progression who receive BCG as a second-line therapy because intravesical chemotherapy has failed to prevent relapse, the high risk of toxicity of maintenance therapy does not justify its use. In this subgroup, it is probably appropriate to use either a 6-week induction course or a 6-week induction followed by three weekly instillations 3 months later. However, if the patient has CIS and/or T 1G3, maintenance therapy is necessary. This is especially true if there were no signs of significant toxicity during the induction course.

Side effects of BCG therapy

BCG therapy can be complicated by side effects. Most of the symptoms that accompany the administration of BCG do not pose a threat to the patient's health, however, there are more serious complications that require immediate treatment. Cystitis, the most common side effect of BCG therapy, occurs in 90% of patients. Dysuria develops as a result of an inflammatory response to BCG therapy not earlier than after 3-4 instillations. Most often, the symptoms of cystitis resolve within 24 hours. Non-steroidal anti-inflammatory and / or anticholinergic drugs can somewhat reduce dysuria. However, if acute irritative symptoms persist for more than 72 hours, isoniazid may be given. Treatment should be continued for 1-2 weeks or until the symptoms of cystitis are relieved. Some urologists recommend isoniazid 300 mg the day before and for 3 days after BCG instillation. BCG should not be administered until all side effects from previous administration have resolved. This is especially important in the development of hematuria, which occurs in 20-35% of patients.

Other non-life-threatening complications (20%) include general weakness, fatigue, and drowsiness. Low-grade fever (less than 38°C) may occur in 10-15% of patients, but it usually resolves within 24 hours. It is important to distinguish these mild short-term side effects from the more serious symptoms of a general infection.

Any patient with a body temperature over 39.5°C should be hospitalized and treated as for BCG sepsis. If treatment is not started on time, sepsis can lead to the death of the patient. Current recommendations for the treatment of BCG sepsis are isoniazid 300 mg, rifampicin 600 mg and prednisone 40 mg per day. Treatment with prednisolone continues until the signs of sepsis are relieved (with subsequent dose reduction within 1-2 weeks), isoniazid and rifampicin - 3-6 months. Patients with a history of BCG sepsis should no longer receive BCG.

Thus, intravesical chemotherapy reduces the short-term recurrence rate in superficial bladder cancer. However, there is no long-term reduction in the recurrence rate, and intravesical chemotherapy does not affect the rate of progression to muscle-invasive tumors. In addition, adjuvant intravesical chemotherapy does not affect survival. Intravesical chemotherapy may be recommended for patients with multiple or frequently recurrent well- and moderately differentiated Ta tumors.

Unlike chemotherapy, BCG immunotherapy, in addition to reducing the frequency of relapses, leads to a decrease in the incidence of tumor progression and increases the survival of patients with SCCM. BCG immunotherapy is indicated in patients at high risk for recurrence and progression of superficial bladder cancer (CIS, stage T). 1, poorly differentiated tumors), as well as in cases of ineffectiveness of intravesical chemotherapy in highly and moderately differentiated Ta tumors.

The limited effectiveness of intravesical chemotherapy and the high toxicity of BCG necessitate the search for new approaches to the prevention of relapses and the treatment of superficial bladder cancer. Such approaches include the use of new chemotherapeutic agents, as well as new immunological agents (interferon-α, interleukin-2, keyhole mollusk hemocyanin), electrophoretic administration of chemotherapeutic agents, the use of photodynamic therapy and intravesical thermochemotherapy. Many of them have shown encouraging results, but more research is needed before a new type of treatment is introduced into clinical practice.

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Attention! The article is addressed to medical specialists. Reprinting this article or its fragments on the Internet without a hyperlink to the original source is considered a copyright infringement.

Anatoly Shishigin

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Chemotherapy for bladder cancer is one of the main treatments for this disease. The impact of drugs on abnormalities in cellular structures is used to improve the outcome of surgical intervention, as well as to reduce the unpleasant symptoms of the disease in cases where the operation is not possible. The technique has many unpleasant consequences, but without it it is very difficult to destroy a neoplasm in cancer.

Features of chemotherapy

Cancer treatment is the introduction into the body of toxic substances that can destroy mutated cells, which leads to the suppression of their activity and growth. Treatment of bladder cancer with antitumor drugs is individual for each patient and consists of several courses, since a single dose of drugs will not have the necessary therapeutic effect.

If an operation is prescribed for a cancer patient, it is always accompanied by chemotherapy, which is carried out both individually and in combination with radiation therapy. The choice is made by the oncologist based on the condition of the patient and the severity of his disease.

As a rule, treatment consists in passing the patient through two stages of therapy:

Preoperative chemotherapy

Doctors call this stage neoadjuvant therapy, it is designed to reduce the size of the tumor in the bladder or in the ureter. This is done to reduce the work during surgery, as well as to reduce the spread of metastases and the success of the operation itself.

Postoperative chemotherapy

Chemotherapy after surgery is called adjuvant chemotherapy and is used to kill cells with a mutation that remained in the bladder after surgery or remained in the bloodstream / lymph flow. This procedure is necessary to prevent the recurrence of the disease.

The maximum effect is achieved in the case of preoperative and postoperative chemotherapy in combination with radiation. Drug treatment can be carried out separately from surgery, this is especially important when cancer metastases spread and grow into neighboring organs. Such metastases are not amenable to surgical removal, so the patient is prescribed orally and intravenously for a long time various chemotherapy drugs of combined action. The course of treatment with such medications continues for several months at short intervals.

During drug therapy against tumors, the improvement should not stop the course of chemotherapy, since abnormal cells remain both in the body and in the lymph flow and circulatory system. One of the important indicators in chemotherapy is the duration of the therapeutic course, which can only be determined by the oncologist treating the patient based on the results of examination and diagnosis.

All chemistry against oncology can be divided into several categories. In order to determine them, it is necessary to conduct additional diagnostics, after which an effective course of therapy is prescribed.

In bladder cancer, the oncologist chooses the necessary chemotherapy drugs against cancer cells that can destroy the tumor as thoroughly as possible. Preference is given to one drug for monochemotherapy, or several for polychemotherapy.

There are four types of direction of drug therapy against the development of tumors.

Systemic chemotherapy

This type of therapy is prescribed for large formations of tumors in the bladder, which have just begun to grow into neighboring organs and lymph nodes. Such treatment is carried out by intramuscular and intravenous administration of the drug, as well as oral administration. Once in the bloodstream, the drug reaches distant sites in the body, which helps to destroy any existing abnormal cells in other tissues.

Intra-arterial chemistry

Drugs with cystic action are injected into the artery near the tumor through a catheter, so that a high concentration of anti-cancer drug is delivered directly to the tumor cell, which reduces its spread and effect on neighboring healthy tissues and cells. This method is still being tested and is not used in all clinics.

Local chemotherapy

Local chemotherapy technique is used for large tumors, as well as for several formations with frequent relapses and aggressive spread in the body. Medicines are administered through a catheter for several hours inside the bladder. Through emptying in a natural way, they are excreted from the body, providing a therapeutic effect along the way. Such intravesical chemotherapy for cancer is done daily for several weeks, effectively acting directly on the neoplasm. After the procedure, the symptoms experienced by the patient are close to the disease of cystitis - frequent urge and pain during urination and so on.

Endolymphatic Chemistry

Anticancer drugs are injected directly into the lymphatics and have a number of advantages over intravenous and intramuscular methods. This technique has proven itself in the complex treatment of patients with oncological diseases. Medicines come through an electric dispenser.

Antitumor techniques can also differ in colors. Depending on the color of the drug, chemistry can be: red, the most powerful, blue, white and yellow. White chemistry is used in the initial stages and is considered the most gentle, but with little therapeutic effect.

The benefits and harms of chemotherapy

For all the benefits of chemotherapy in the fight against cancer, the toxic drugs taken are of great harm to the general condition of the patient.

Advantages

The undoubted advantages of chemotherapy include:

• complete destruction of abnormal cells;
• control over the development of cancer, since all chemotherapy drugs slow down the growth of cells with a mutation. Oncologists can track their spread and destroy new foci of cancer in time;
• reduction of painful symptoms in bladder cancer due to a decrease in the size of the carcinoma, this reduces the pressure of the neoplasm on the nerve endings and muscle structures in the organ;
• Chemotherapy can be combined with radiation and surgery.

Flaws

All the advantages of chemotherapy drugs that fight cancer cells indicate that endolymphatic, systemic and local or intravesical chemotherapy for bladder cancer in men is an effective method of fighting cancer. For a chance at recovery, patients pay large sums of money, although there is no guarantee of recovery.

Often, highly toxic drugs prolong the patient's life by only a couple of months, and in some cases even reduce the remaining time and bring death closer. The consequences are due to increased growth of metastases in the body, since chemotherapy drugs destroy not only mutated cells, but also healthy ones that are in the division stage next to malignant ones.

Anticancer drugs have an extremely negative effect on the reproductive and digestive functions of the body, as well as on the bone marrow, which produces red blood cells. Many complications make such an effect of chemistry on the human body fatal.

Despite all the harm from chemotherapy, you should not refuse such an opportunity, since many drugs with adverse reactions can prolong a person's life. It is important to strictly follow all the recommendations of a doctor who selects regimens and courses of treatment based on the characteristics of the human body, the stage of tumor development and the intensity of its spread.

Preparation and administration of chemotherapy

The detection of oncology in a patient indicates a decrease in the depletion of immune forces and the physical condition of the body. The body's resources wear out, so the patient needs special preparation before chemotherapy. First of all, you need to take sick leave or vacation, which will minimize any physical activity of a person. It is necessary to follow all the recommendations of the oncologist, namely:

• undergo a medical course of treatment in accordance with the identified pathology;
• carry out cleaning of toxins and toxins that linger in the body due to the decay of the tumor. This contributes to the maximum effect when taking anticancer drugs;
• protect the organs of the gastrointestinal tract, urinary system, as well as the liver with the help of medicines and supplements on the recommendation of a specialist;
• conduct moral preparation by communicating with people who have undergone chemotherapy and highly specialized psychologists.

Chemotherapy is carried out in a hospital under the supervision of an oncologist. In this case, the doctor can monitor the administration of chemotherapy drugs and adjust the dosage, if necessary.

For bladder cancer, systemic chemotherapy is allowed on an outpatient basis. All drugs that need to be taken orally, the patient can drink at home, arriving at the clinic for intramuscular and intravenous injections, testing for laboratory tests and examination by an oncologist.

If there is a need for a long course, a catheter is inserted into the patient's vein to save the vein itself and avoid additional injury. Also, a catheter is needed in order to prevent infection.

Schemes and courses of therapy

After diagnosing bladder cancer and making an accurate diagnosis, the specialist selects a special treatment protocol, which indicates chemotherapy drugs. It consists in the selection of individual drugs for the patient and the regimen for their administration. Most often, antitumor agents are used in medicine, such as Ftorafur Cyclophosphamide, Cisplatin, Methotrexate, Adriamycin, Mitomycin, Bleomycin.

The dosage is selected based on the severity of the disease and the degree of spread of oncology. The name of the scheme is given from the first letters of the Latin name of the drug.

A typical four-drug regimen is the MVAC regimen.

M (methotrexate), V (vinblastine), A (doxorubicin), and C (cisplatin).

In this case, it is possible to exclude the components and replace them with analogues, since Doxorubicin is not allowed for use in heart diseases, and Cisplatin is prohibited for patients with a diseased kidney. Bladder chemotherapy is supplemented with radiation therapy, courses last from 3 to 6 months with a small interval of 2 to 4 weeks.