Does chemotherapy help lung cancer? Lung cancer treatment with chemotherapy. Modern tactics of SCLC treatment

Treatment with cytostatic drugs is a common practice in oncology. Chemotherapy for lung cancer is proposed as the main treatment, in parallel, drugs can be recommended to reduce the side effects of essential drugs.

The procedure involves the introduction of anticancer drugs through a dropper. During treatment, it is possible to completely destroy the tumor or stop its growth.

“Chemistry” also makes it possible to prevent metastasis and avoid relapses. The effectiveness of treatment is determined by the age of the patient, the body's resistance and the degree of the disease. Unfortunately, it is difficult to achieve high therapeutic results in stage IV cancer. Positive dynamics is observed only in 10% of cases. With progressive oncology, treatment with cytostatic drugs is supplemented with radiation therapy, which allows you to stop the spread of metastases and preserve the functionality of vital organs.

Drugs used during chemotherapy for lung cancer

The therapy regimen is selected individually. In this regard, there are several main treatment options, which are determined by the color of the drugs:

Red - is considered the most toxic, causes a sharp weakening of immunity and adversely affects the state of healthy cells in the body. Implies the use of anthracyclines, which have a red tint.
Yellow - less aggressive, implies the use of drugs such as "Cyclophosphamide", "Fluorouracil", "Methotrexate".
Blue - gives good results in the initial stages of oncology. Blue chemotherapy involves the use of Mitomycin and Mitoxantrone.
White - during the treatment, such drugs as Taxotere and Taxol are used.

There is no universal method of treatment, therefore, mixed regimens are used to increase the effectiveness of therapy.

Treatment in Ukraine will cost around 20,000-90000 hryvnia. State programs for the treatment of cancer patients provide for a reduction in the cost of chemotherapy through the use of some budget drugs and free procedures.

A course of chemotherapy in the United States will cost $ 250-2000. The cost is determined by the severity of the disease and the characteristics of the treatment course. Traditionally, Israeli clinics show the best results. The starting price for treatment is $ 1,600.

Lifestyle during and after chemotherapy for lung oncology

For the period of treatment, the patient's lifestyle does not fundamentally change. You will definitely have to give up alcohol, heavy food and products containing carcinogens. It is also necessary to refrain from sun exposure, thermal treatments and physiotherapy.

Since chemotherapy negatively affects the state of the immune system, the patient should increase the intake of foods containing vitamin C. However, vitamin therapy should be approached with extreme caution, since some compounds can provoke the activity of pathological cells.

In the case of a cold during treatment with cytostatics, the doctor may prescribe antibacterial and sulfa drugs, as well as herbal remedies to strengthen the immune system.

Possible consequences

Since chemotherapy for lung cancer is characterized by a high degree of aggressiveness, the risk of side effects and complications remains quite high. The toxic effect of drugs can cause the following negative consequences:

noise in ears;
focal or total;
loss of limb sensitivity;
nausea, weakness, dizziness;
changes in blood composition;
decreased appetite and problems with the gastrointestinal tract;
hearing impairment.

Usually, when side effects appear, adjustments are made to treatment, but this rule does not work for chemotherapy. The main task of treatment is to stop the growth of a cancerous tumor and, if possible, destroy it. Only after the desired result is achieved, procedures can be carried out to restore the body. If complications arise during the treatment period, adaptogen agents can be recommended.

Serious consequences include bone weakening, which leads to osteoporosis. Similar manifestations occur in a mixed treatment regimen, when drugs such as Cyclophosphamide and Fluorouracil are used.

The side effects of the treatment can also include hormonal imbalance, which is especially annoying for women. Due to hormonal problems, the menstrual cycle gets lost and the ovaries are disrupted.

After the end of the treatment course, most of the side effects disappear. Some patients begin to notice improvements already in the later stages of therapy.

Today chemotherapy for lung cancer is the most effective and reliable method for treating advanced tumors. As you can see, the best results are obtained by combined treatment regimens using cytostatics of various groups.

Lung cancer ranks first in the number of deaths among all cancers. The main risk group is the elderly, but the disease is also diagnosed in young patients.

Chemotherapy for lung cancer is the main method of fighting cancer cells. In the first two stages of the disease, "chemistry" can be combined with operations to remove tumors.

At the third stage, when the metastasis of cancer cells begins, the administration of chemotherapy drugs becomes the main focus and can be combined with radiation therapy.

Diagnosis of lung cancer means that the patient is developing tumor formations in the respiratory system. Most often, the tumor is localized in the right lung, in its upper lobe.

Fact! The difficulty in treatment lies in the asymptomatic course of the disease in the initial stages. They diagnose it when metastasis begins, and pathogenic cells spread to other organs.

Chemotherapy treatment of lung cancer is the main method of combating this oncology. It consists in the fact that the patient is injected with drugs that stop the growth of cancer cells, prevent them from dividing and ultimately destroy them completely. Drug treatment can be used as the only method, but in some cases it can be combined with radiation therapy or surgical removal tumors.

The most effective "chemistry" fights small cell cancer, which is quite noticeably susceptible to drugs. The non-small cell structure of the tumor often shows resistance and a different course of treatment is selected for the patient.

The spread of cancer cells to other organs means metastasis of the disease and the progression of stage 4 cancer. It is not possible to fight metastases with the help of chemotherapy drugs. Therefore, at stage 4, drug therapy is used as palliative treatment.

Treatment process

Modern medicine has made the process of prescribing drugs much more complicated. Even 10-15 years ago, everything was much simpler: a patient with oncology comes to the clinic and he is prescribed one or two drugs, depending on his condition.

The treatment instructions for almost all categories of patients were the same. Neither histological results nor biological indicators were taken into account, the opinion of doctors from other fields of medicine was not taken into account - all this did not affect the course of treatment.

The chemotherapy procedure at the present stage, for patients with lung cancer, will be carried out depending on the disease itself.

Tumor indicators affecting the course of treatment:

the size of the tumor;
stage of development;
the level of metastasis;
progression and growth rate;
location of localization.

The individual indicators of the organism have an effect on the course of therapy:

age;
general health;
the presence of chronic pathologies;
the state of the body's immune system.

In addition to indicators of the development of oncology and the individual characteristics of the organism, modern clinics take into account the cytogenetics of the tumor. Depending on this indicator, cancer patients are divided into four groups and appropriate treatment is prescribed.

Attention! Taking into account narrowly targeted indicators, coupled with the latest medical advances, has significantly increased the percentage of complete recovery. It is worth noting that these statistics confirm the positive results obtained at the initial stages of tumor development.

How is chemotherapy for lung cancer treated?

The course of treatment of cancer patients is adjusted by an oncologist. The individual characteristics of the body, the structure of the tumor, the stage of the disease - these factors will affect how chemotherapy is carried out for lung cancer.

Treatment with medicines is carried out on an outpatient basis. Medicines are taken orally or intravenously. The oncologist selects the dosage and drug for the patient, having previously summed up all the factors of the disease. Combination tactics are commonly used. This is practiced for more effective treatment.

Cancer is treated with drugs in cycles of several weeks or months. The interval between cycles is 3 to 5 weeks. This rest is very important for a cancer patient. It allows the body and the immune system to recover from chemotherapy.

There is a possibility of adaptation of cancer cells to active drugs. To avoid reducing the effectiveness of treatment, drugs are replaced. Modern pharmacology has come close to solving the problem of reducing the effect of drugs on tumor formations. The latest generations of cancer drugs should not have an addictive effect.

During chemotherapy, the patient's general condition worsens, side effects manifest themselves. The attending physician must constantly monitor the patient's health. Regular examination and monitoring of vital signs is important.

The number of cycles depends primarily on the effectiveness of the treatment. The most acceptable for the body is 4-6 cycles. This avoids a serious deterioration in the patient's well-being.

Important! Chemotherapy procedures should be carried out in conjunction with therapy aimed at reducing side effects.

Contraindications to chemotherapy for lung cancer

Chemotherapy for lung cancer is defined as the most effective method of fighting cancer. It is used when there are contraindications to other methods of treatment, for example, to surgery. But there are a number of factors, in the presence of which drug-induced destruction of cancer cells is contraindicated.

The main list of contraindications is as follows:

metastasis to the liver or brain;
intoxication of the body (for example, severe pneumonia, etc.);
cachexia (complete exhaustion of the body with weight loss);
an increased level of bilirubin (indicates the active destruction of red blood cells).

To prevent a harmful effect on the body, a number of studies are carried out before chemotherapy. Only after the results are obtained, a medication course is selected.

Side effects and complications

Drug treatment of a tumor is aimed at inhibiting the division of cancer cells or completely destroying them. However, along with the positive effect of such therapy, almost all patients have many complications.

First of all, the toxic effects of drugs come under attack: the immune system, gastrointestinal tract, hematopoiesis.

Consequences of chemotherapy for lung cancer:

diarrhea, nausea, vomiting;
hair loss;
destruction of cells of leukocytes, erythrocytes, platelets;
accession of side infections;
fast fatiguability;
nails become brittle;
headaches and drowsiness;
violation of hormonal levels (women especially suffer).

If complications appear during the treatment period, first of all, it is necessary to contact your doctor and get tested. After receiving the clinical analysis, the specialist will be able to correct the exposure regimen.

It is worth noting the fact that the doctor must be informed about the manifestation of side effects. The doctor will be able to choose the symptomatic treatment. Select methods of dealing with side effects independently - is prohibited.

Drugs used in the treatment of lung cancer

Medicines that work to fight cancer cells have different efficacy and tolerance. The world's leading cancer control centers are constantly developing the latest methods of therapy with greater precision and focus.

Drugs for chemotherapy for lung cancer are used taking into account a large number of individual patient factors. Also, medications are prescribed, taking into account the degree of their effect on pathogenic cells and the stage of development of the disease.

Fixed assets are discussed in the table:

Drug groups	The mechanism of action on cancer cells.	Active ingredients	Side effects
Alkating agents	They interact with DNA, resulting in cell mutation and death.	Cyclophosphamide, Embikhin, Nitromozoureas	Gastrointestinal tract, hematopoiesis (leukopenia, thrombocytopenia).
Antimetabolites	They inhibit biochemical processes, causing a slowdown in cell growth and impairment of their functions.	Folurin, Nelarabin, Fopurin, Cytarabine, Methotrexate	Stomatitis, oppression of hematopoiesis, spontaneous bleeding, infections.
Anthracyclines	They act on a DNA molecule, causing a violation of replication. They have a mutagenic and carcinogenic effect on the cell.	Daunomycin, Doxorubicin.	Cardiotoxicity. Development of irreversible cardiomyopathy.
Vincaloids	Affects the protein tubulin, which is part of microtubules, and leads to their disappearance.	Vinblastine, Vinkrestin, Vindesine	Tachycardia, anemia, paresthesia, hyperesthesia.
Platinum preparations	They destroy the DNA of cancer cells and inhibit their growth.	Cisplatin, Finatriplatin, Carboplatin, Platinum.	Thrombocytopenia, anemia, leukopenia, impaired liver function, allergic reactions.
Taxanes	Prevents cancer cell division	Docetaxel, Paclitoxel Taxotere	Decrease in blood pressure, vascular thrombosis, anorexia, asthenia, anemia.

Modern chemotherapy provides more and more positive guarantees and is less painful for patients. At this stage in the development of medicine, there are no anticancer drugs without side effects. A common side feature that unites almost all chemotherapy drugs is the effect on the gastrointestinal tract and hematopoietic organs.

The video in this article will acquaint readers with the peculiarities of chemotherapy and the principle of influence.

Chemotherapy diet

During the fight against a tumor in the lungs, the patient's body is literally depleted. This is the price the patient pays to destroy cancer cells. Drug treatment is not accompanied by a special appetite. Food for the body becomes the only source of minerals and vitamins replenishment.

Nutrition after chemotherapy for lung cancer is not special. Rather, it should be balanced and healthy (pictured). Much of what the patient could afford before treatment will have to be excluded from the diet.

canned foods;
sweets and confectionery;
fatty and spicy foods;
food in the base, which can be low quality meat (sausages, smoked meats);
alcohol;
coffee.

Chemotherapy has a detrimental effect on proteins in the body. Therefore, special attention should be paid to foods containing proteins. Such food will significantly speed up the recovery process of the body.

Foods to include in the diet:

containing protein - nuts, chicken, eggs, legumes;
containing carbohydrates - potatoes, rice, pasta;
dairy products - cottage cheese, kefir, fermented baked milk, yoghurts;
seafood - lean fish, blue algae;
vegetables and fruits in any form;
drinking plenty of fluids removes toxins from the body.

Important! Lung cancer patients undergoing chemotherapy should seek advice from a dietitian. It is necessary to understand a very important aspect: nutrition is a very important factor affecting the general condition and speedy recovery of a cancer patient.

Survival prognosis for lung cancer patients after chemotherapy

The question of life expectancy after chemotherapy procedures is fundamental. Of course, every patient with oncology hopes for a positive result.

The prognosis for survival depends on many factors. But the most important of these is the stage of the disease at which the patient will be treated. The proportion is obvious - the higher the stage, the lower the percentage of survival and life expectancy.

Important! The likelihood of a favorable outcome may directly depend on the form of pathology.

Small cell carcinoma is the most common and aggressive, the pathology of this form has a negative prognosis. Life expectancy after chemotherapy for lung cancer with this form increases by about 5 times, but the prognosis in most cases remains poor.

Only 3% of patients will live more than 5 years. The average life expectancy is 1 to 5 years. Relapse of oncology after chemotherapy worsens the patient's prognosis.

Non-small cell cancers are mostly treated with surgery. Chemotherapy is given after the tumor has been removed. The prognosis for NCCLC is more favorable - 15% of patients will live 5 years. The average life expectancy is 3 years.

If metastasis has spread to other organs, then even the most advanced drugs at stage 4 of the disease are powerless. Cancer cells are not sensitive to them and chemotherapy is performed as a palliative treatment.

Despite all the difficulties endured by the patient during chemotherapy, one cannot refuse it. Modern techniques can significantly extend a person's life and make it better. Whatever the statistics on lung cancer, no one can determine exactly how long a patient will live.

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PRACTICAL ONCOLOGY. Vol.6, No. 4 - 2005

GU RONTs them. N.N.Blokhina RAMS, Moscow

M.B. Bychkov, E.N. Dgebuadze, S.A. Bolshakova

Research on new therapies for SCLC is underway. On the one hand, new regimens and combinations with lower levels of toxicity and greater efficacy are being developed; on the other hand, new drugs are being studied. The main goal of the ongoing research is to increase patient survival and reduce the frequency of relapses. It is necessary to continue studying the effectiveness of new drugs with a new mechanism of action.

Lung cancer is one of the most common cancers in the world. Non-small cell (NSCLC) and small cell (SCLC) forms of lung cancer occur in 80-85% and 10-15% of cases, respectively. As a rule, its small-cell form is most often found in smokers and very rarely in non-smokers.

SCLC is one of the most malignant tumors and is characterized by a short history, a rapid course, and has a tendency to early metastasis. Small cell lung cancer is a tumor that is highly sensitive to chemotherapy, and in most patients, an objective effect can be obtained. When a complete tumor regression is achieved, prophylactic irradiation of the brain is performed, which reduces the risk of distant metastasis and increases the overall survival rate.

In the diagnosis of SCLC, the assessment of the prevalence of the process, which determines the choice of therapeutic tactics, is of particular importance. After morphological confirmation of the diagnosis (bronchoscopy with biopsy, transthoracic puncture, biopsy of metastatic nodes), computed tomography (CT) of the chest and abdomen, as well as CT or magnetic resonance imaging (MRI) of the brain (with contrast) and bone scanning are performed.

Recently, there have been reports that positron emission tomography makes it possible to further refine the stage of the process.

In SCLC, as in other forms of lung cancer, staging according to the international TNM system is used, however, most patients with SCLC already have stage III-IV disease at the time of diagnosis; therefore, the classification, according to which they are distinguished, has not lost its significance until now. localized and widespread forms of the disease.

In the localized stage of SCLC, the tumor lesion is limited to one hemithorax with the involvement of the regional ipsilateral lymph nodes of the root and mediastinum, as well as the ipsilateral supraclavicular lymph nodes, when technically it is possible to perform irradiation using one field.

A common stage of the disease is the process when the tumor lesion is not limited to one hemithorax, with the presence of contralateral lymphogenous metastases or tumor pleurisy.

The stage of the process that determines therapeutic options is the main prognostic factor in SCLC.

Prognostic factors:

1. The degree of prevalence of the process: in patients with a localized process (not beyond the chest), the best results are achieved with chemoradiation therapy.

2. Achievement of complete regression of the primary tumor and metastases: there is a significant increase in life expectancy and there is a possibility of complete recovery.

3. The general condition of the patient: patients who begin treatment in good condition have a higher treatment efficiency, greater survival rate than patients in a serious condition, exhausted, with severe symptoms of the disease, hematological and biochemical changes.

Surgical treatment is indicated only in the early stages of SCLC (T 1-2 N 0-1). It should be supplemented with postoperative polychemotherapy (4 courses). In this group of patients5 -year survival rate is39 % [ 33 ].

Radiation therapy leads to tumor regression in 6080% of patients, however, in an independent form, it does not increase life expectancy due to the appearance of distant metastases [9 ].

Chemotherapy is the cornerstone of SCLC treatment. Among the active drugs, it should be noted: cyclophosphamide, doxorubicin, vincristine, etoposide, topotecan, irinotecan, paclitaxel, docetaxel, gemcitabine, vinorelbine. Their effectiveness in monotherapy ranges from 25 to 50%. Table 1 shows the schemes of modern combined chemotherapy for SCLC.

The effectiveness of modern therapy for this form of SCLC ranges from 65% to 90%, with complete tumor regression in 45-75% of patients and a median survival rate of 1824 months. Patients who begin treatment in good general condition (PS 0-1) and respond to induction therapy have a 5-year disease-free survival rate.

In the case of a localized form of SCLC, chemotherapy (CT) is carried out according to one of the above schemes (2-4 courses) in combination with radiation therapy (RT) to the area of \u200b\u200bthe primary focus, the root of the lung and mediastinum, with a total focal dose of 30-45 Gy (50-60 Gr by isoeffect). The start of radiation therapy should be as close as possible to the start of chemotherapy, i.e. It is best to start RT either with 1–2 courses of chemotherapy or after evaluating the effectiveness of treatment for two courses of CT.

Patients who have achieved complete remission are recommended to carry out prophylactic brain irradiation in a total dose of 30 Gy due to the high risk (up to 70%) of brain metastases.

The median survival rate for patients with localized SCLC using combined treatment is 16-24 months, while the 2-year survival rate is 40-50%, and the 5-year survival rate is 10%. In the group of patients who started treatment in good general condition, the chances of achieving a 5-year survival rate are 25%.

In such patients, the main method of treatment is combined chemotherapy in the same modes, and radiation is carried out only for special indications. The overall effectiveness of chemotherapy is 70%, but complete regression is achieved in only 20% of patients. At the same time, the survival rate of patients when a complete tumor regression is achieved is significantly higher than when a partial regression is obtained, and approaches the survival rate of patients with a localized form of SCLC.

Table # 1.

Schemes of modern combined chemotherapy for SCLC

Drugs	Chemotherapy regimen	Interval between courses
EP Cisplatin Etoposide	80 mg / m2 IV on day 1 120 mg / m2 IV on days 1,2,3	1 time in 3 weeks
CDE Cyclophosphamide Doxorubicin Etoposide	1000 mg / m2 IV on the 1st day 45 mg / m2 IV on the 1st day 100 mg / m2 IV on the 1,2,3th days or 1,3,5th days	1 time in 3 weeks
CAV Cyclophosphamide Doxorubicin Vincristine	1000 mg / m2 IV on day 1 50 mg / m2 IV on day 1 1.4 mg / m2 IV on day 1	1 time in 3 weeks
AVP Nimustin (CCNU) Etoposide Cisplatin	2-3 mg / kg IV on the 1st day 100 mg / m2 IV on the 4,5,6th days 40 mg / m2 IV on the 1,2,3th days	1 time in 4-6 weeks
CODE Cisplatin Vincristine Doxorubicin Etoposide	25 mg / m2 IV on day 1 1 mg / m2 IV on day 1 40 mg / m2 IV on day 1 80 mg / m2 IV on days 1, 2, 3	Once a week for 8 weeks
TC Paclitaxel Carboplatin	135 mg / m2 IV on day 1 AUC 5 mg / m2 IV on day 1	1 time in 3-4 weeks
TP Docetaxel Cisplatin	75 mg / m2 IV on day 1 75 mg / m2 IV on day 1	1 time in 3 weeks
IP Irinotecan Cisplatin	60 mg / m2 IV on days 1,8,15 60 mg / m2 IV on day 1	1 time in 3 weeks
GP Gemcitabine Cisplatin	1000 mg / m2 IV on days 1.8 70 mg / m2 IV on day 1	1 time in 3 weeks

With metastatic lesions of the bone marrow, distant lymph nodes, with metastatic pleurisy, chemotherapy is the main method of treatment. In case of metastatic lesions of the lymph nodes of the mediastinum with a syndrome of compression of the superior vena cava, it is advisable to use combined treatment (chemotherapy in combination with radiation). For metastatic lesions of bones, brain, adrenal glands, radiation therapy is the method of choice. In case of brain metastases, radiation therapy in a total focal dose (SOD) of 30 Gy allows to obtain a clinical effect in 70% of patients, and in half of them complete tumor regression is recorded according to CT data. Recently, there have been reports of the possibility of using systemic chemotherapy for brain metastases. Table 2 presents the modern tactics of treatment of various forms of SCLC.

Despite the high sensitivity to chemotherapy and radiation therapy for SCLC, this disease has a high relapse rate; in this case, the choice of drugs for second-line chemotherapy depends on the level of response to the first line of treatment, the duration of the relapse-free interval, and the localization of metastatic foci.

It is customary to distinguish between patients with a sensitive relapse of SCLC, i.e. who had a history of full or partial effect from the first line of chemotherapy and the presence of progression after at least3 months after the end of induction chemotherapy. In this case, it is possible to reuse the treatment regimen against which the effect was revealed. There are patients with refractory relapse, i.e. when the disease progresses during the first line of chemotherapy or in less than3 month after its completion. The prognosis of the disease in patients with SCLC is especially unfavorable for patients with refractory relapse - in this case, the median survival rate after the diagnosis of relapse does not exceed 3-4 months. In the presence of refractory relapse, it is advisable to use previously unused cytostatics and / or their combinations.

Recently, new drugs have been studied and are already being used in the treatment of SCLC, such as gemcitabine, topotecan, vinorelbine, irinotecan, taxanes, as well as targeted drugs.

Gemcitabine. Gemcitabine is an analogue of deoxytidine and belongs to pyrimidine antimetabolites. According to research by Y. Cornier et al., Its effectiveness in monotherapy was 27%, according to the results of a Danish study, the level of overall effectiveness is 13%. Therefore, they began to study combined chemotherapy regimens with the inclusion of gemcitabine. In an Italian study, the PEG regimen (gemcitabine, cisplatin, etoposide) was carried out, with an objective efficacy rate of 72%, but high toxicity was noted. London Lung Group has published data from a randomized phase III trial head-to-head comparison between GC (gemcitabine + cisplatin) and PE. There were no differences in medians of survival, and a high level of toxicity of the GC regimen was also noted.

Topotecan. Topotecan is a water-soluble drug that is a semi-synthetic analogue of camptothecin, it does not cross-toxicity with other cytostatics used in the treatment of SCLC. The results of some studies indicate its effectiveness in the presence of resistant forms of the disease. Also, these studies revealed a good tolerance of topotecan, characterized by controlled noncumulative myelosuppression, a low level of non-hematological toxicity, and a significant decrease in the clinical manifestations of the disease. The use of topotecan as a second-line treatment for SCLC is approved in approximately 40 countries worldwide, including the United States and Switzerland.

Vinorelbin. Vinorelbine is a semi-synthetic vinca alkaloid, which is involved in the prevention of tubulin depolymerization processes. According to some studies, the response rate with vinorelbine monotherapy is 17%. It was also found that the combination of vinorelbine and gemcitabine is quite effective and has a low level of toxicity. J.D. Hainsworth et al. the partial regression rate was 28%. Several research groups have evaluated the efficacy and toxic profile of the combination of carboplatin and vinorelbine. The data obtained indicate that this scheme is actively working in small cell lung cancer, however, its toxicity is quite high, and therefore, it is necessary to determine the optimal doses for the above combination.

Table 2.

Modern tactics of SCLC treatment

Irinotecan. Based on results from a Phase II studyJapan Clinical Oncology Group started a randomized phase III trialJCOG -9511 by direct comparison of two chemotherapy regimens cisplatin + irinotecan (PI ) and cisplatin + etoposide (PE) in previously untreated patients with SCLC. In the first combination, the dose of irinotecan was60 mg / m 2 in 1, 8 th and 15th days, cisplatin -60 mg / m 2 on the 1st day every 4 weeks, in the second combination, cisplatin was administered at a dose of 80 mg / m 2 , etoposide - 100 mg / m 2 on days 1-3, every 3 weeks. In total, in the first and second groups,4 chemotherapy course. It was planned to include 230 patients in the work, however, the recruitment was stopped after a preliminary analysis of the results obtained (n \u003d 154), since there was a significant increase in survival in the group receiving treatment according to the schemePI (the median of survival is12.8 vs.9.4 months, respectively). However, it should be noted that only 29% of patients randomized to the groupPI , were able to receive the required dose of drugs. According to this study, the schemePI was recognized in Japan as the standard treatment for localized forms of SCLC. Due to the small number of patients, the data of this work had to be confirmed.

Therefore, a study was initiated in North AmericaIII phase. Taking into account the results already available, the doses of the drugs were reduced. In the schemePI the dose of cisplatin was30 mg / m 2 in 1 1st day, irinotecan- 65 mg / m 2 in 1st and 8th th days of a 3-week cycle. In terms of toxicity, grade IV diarrhea has not been reported, preliminary efficacy data are pending.

Taxanes. In the work of J. E. Smyth et al. the efficacy of docetaxel was studied100 mg / m 2 in monotherapy in previously treated patients (n \u003d 28), the objective efficiency was 25% [32 ].

Into the ECOG study included 36 previously untreated SCLC patients who received paclitaxel 250 mg / m 2 as a 24-hour infusion every 3 weeks. The level of partial regression was30%, at 56 Grade IV leukopenia was registered in% of cases. However, interest in this cytostatic did not wane, and therefore, in the USA,Intergroup Study where the combination of paclitaxel with etoposide and cisplatin (TEP) or carboplatin - (TEC) was studied. In the first group, chemotherapy was performed according to the TEP regimen (paclitaxel 175 mg / m 2 in 1 day, etoposide 80 mg / m 2 in 1 - 3 days and cisplatin 80 mg / m 2 in 1 day, with a prerequisite for the introduction of colony-stimulating factors from the 4th to the 14th days), in the PE regimen the doses of drugs were identical. A higher level of toxicity was observed in the TEP group, unfortunately, no differences in median survival were obtained (10.4 versus 9.9 months).

M. Reck et al. provided data from a randomized trialIII phase in which the combination of TEC (paclitaxel 175 mg / m 2 on the 4th day, etoposide in1 - 3 days at a dose of 125 mg / m 2 and 102.2 mg / m2 for patients with I - IIffi and stage IV disease, respectively, and carboplatinAUC 5 on the 4th day), in another group -CEV (vincristine 2 mg in the 1st and8 1st days, etoposide from 1st to 3rd day at a dose of 159 mg / m 2 and 125 mg / m 2 patients with stage I-III and IV and carboplatinAUC 5 on the 1st day). The median overall survival was 12.7 versus 10.9 months, respectively; however, the differences obtained are not significant (p \u003d 0.24). The level of toxic reactions was approximately the same in both groups. According to other studies, similar results were not obtained, so today taxane drugs are rarely used in the treatment of small cell lung cancer.

In the treatment of SCLC, new directions of drug treatment are being investigated, which tend to move from nonspecific drugs to the so-called targeted therapy aimed at certain genes, receptors, and enzymes. In the coming years, it is the nature of molecular genetic disorders that will determine the choice of drug treatment regimens in patients with SCLC.

Targeted therapy aHmu-CD56. It is known that small cell lung cancer cells expressCD 56. It is expressed by peripheral nerve endings, neuroendocrine tissues, and myocardium. To suppress expressionCD 56 conjugated monoclonal antibodies were obtainedN 901- bR ... Patients (n \u003d 21 ) with relapse of SCLC, they were infused for 7 days. In one case, partial tumor regression was registered, the duration of which was 3 months. In workBritish Biotech (I phase) studied monoclonal antibodiesmAb which are conjugated to the toxinDM 1.DM 1 inhibits the polymerization of tubulin and microtubules, which leads to cell death. Research in this area is ongoing.

Thalidomide. It is believed that the growth of solid tumors depends on the processes of neoangiogenesis. Taking into account the role of neoangiogenesis in the growth and development of tumors, drugs are being developed aimed at stopping the processes of angiogenesis.

For example, thalidomide was known as a drug for insomnia, which was subsequently discontinued due to its teratogenic properties. Unfortunately, the mechanism of its antiangiogenic action is not known, however, thalidomide blocks vascularization processes induced by fibroblast growth factor and endothelial growth factor. In the II phase of the study, 26 patients with previously untreated SCLC underwent6 courses of standard chemotherapy according to the RE regimen, and then for 2 years they received thalidomide treatment(100 mg per day) with minimal toxicity. In 2 patients, PR was registered, in 13 - HR, the median survival was 10 months, 1-year survival was 42%. Taking into account the obtained promising results, it was decided to start researchIII phases for the study of thalidomide.

Matrix metalloproteinase inhibitors. Metalloproteinases are important enzymes involved in neoangiogenesis, their main role is participation in the processes of tissue remodeling and continued tumor growth. As it turned out, tumor invasion, as well as its metastasis, depend on the synthesis and release of these enzymes by tumor cells. Some inhibitors of metalloproteinases have already been synthesized and tested in small cell lung cancer, such as marimastat (British Biothech) and BAY 12-9566 (Bayer).

More than 500 patients with localized and disseminated forms of small cell lung cancer participated in a large study of marimastat; after chemotherapy or chemoradiation, one group of patients was prescribed marimastat (10 mg 2 times a day), the other - placebo. It was not possible to obtain an increase in the survival rate. In the studyBAY 12-9566 in the study drug group, a decrease in survival was noted, therefore, studies of metalloproteinase inhibitors in SCLC were discontinued.

Also, in SCLC, a study of drugs was carried outinhibiting tyrosine kinase receptors (gefitinib, imatinib) ... Only in the study of imatinib (glivec) promising results were obtained, and therefore, work continues in this direction.

Thus, in conclusion, it should be emphasized once again that research is currently underway on new methods of therapy for SCLC. On the one hand, new regimens and combinations with lower levels of toxicity and greater efficacy are being developed; on the other hand, new drugs are being studied. The main goal of the ongoing research is to increase patient survival and reduce the frequency of relapses. It is necessary to continue studying the effectiveness of new drugs with a new mechanism of action. This review presents the results of several studies that reflect evidence from chemotherapy and targeted therapy. Targeted drugs have a new mechanism of action, which gives reason to hope for the possibility of more successful treatment of such a disease as small cell lung cancer.

Literature

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In the structure of oncological diseases, lung cancer is one of the most common pathologies. It is based on a malignant degeneration of the epithelium of the lung tissue, a violation of air exchange. The disease is characterized by high mortality. The main risk group is male smokers aged 50-80 years. A feature of modern pathogenesis is a decrease in the age of primary diagnosis, an increase in the likelihood of lung cancer in women.

Small cell carcinoma is a malignant tumor that has the most aggressive course and widespread metastasis. This form accounts for about 20-25% of all types. Many scientific experts regard this type of tumor as a systemic disease, in the early stages of which it is almost always present in the regional lymph nodes. , suffer from this type of tumor most often, but the percentage of cases increases significantly. Almost all patients have a fairly severe form of cancer, this is due to rapid growth tumor and wide metastasis.

Small cell lung cancer

The reasons for the development of small cell lung cancer

In nature, there are many reasons for the development of a malignant neoplasm in the lungs, but there are main ones that we encounter almost every day:

smoking;
exposure to radon;
asbestosis of the lungs;
viral damage;
dust exposure.

Clinical manifestations of small cell lung cancer

Small cell lung cancer symptoms:

a cough of a prolonged nature, or a reappearing cough with changes usual for the patient;
lack of appetite;
weight loss;
general malaise, fatigue;
shortness of breath, pain in the chest and lungs;
change in voice, hoarseness (dysphonia);
pain in the spine with bones (occurs with bone metastases);
epileptic seizures;
lung cancer, stage 4 - speech impairment occurs and severe headaches appear.

Small cell lung cancer grades

Stage 1 - tumor size up to 3 cm in diameter, the tumor has affected one lung. There is no metastasis.
Stage 2 - the size of the tumor in the lung is from 3 to 6 cm, blocks the bronchus and grows into the pleura, causes atelectasis;
Stage 3 - the tumor rapidly passes into neighboring organs, its size has increased from 6 to 7 cm, atelectasis of the entire lung occurs. Metastases in adjacent lymph nodes.
Stage 4 small cell lung cancer is characterized by the spread of malignant cells to distant organs of the human body and causes symptoms such as:

headaches;
hoarseness or loss of voice at all;
general malaise;
loss of appetite and a sharp decrease in weight;
back pain, etc.

Diagnostics of the small cell lung cancer

Despite all clinical examinations, history taking and listening to the lungs, a high-quality one is also needed, which is carried out using such methods as:

skeletal scintigraphy;
chest x-ray;
detailed, clinical blood test;
computed tomography (CT);
liver function tests;
magnetic resonance imaging (MRI)
positron emission tomography (PET);
sputum analysis (cytological examination to detect cancer cells);
pleurocentesis (taking fluid from the chest cavity around the lungs);
- the most common method for diagnosing a malignant neoplasm. It is carried out in the form of removing a particle of a fragment of the affected tissue for further examination under a microscope.

There are several ways to conduct a biopsy:

bronchoscopy combined with biopsy;
performed using CT;
endoscopic ultrasound with biopsy;
mediastinoscopy combined with biopsy;
open lung biopsy;
pleural biopsy;
video thoracoscopy.

Small cell lung cancer treatment

The most important place in the treatment of small cell is chemotherapy. In the absence of appropriate treatment for lung cancer, the patient dies 5-18 weeks after diagnosis. Polychemotherapy helps to increase the mortality rate to 45 - 70 weeks. They use it, both as an independent method of therapy, and in combination with surgery or radiation therapy.

The goal of this treatment is complete remission, which must be confirmed by bronchoscopic methods, biopsy and bronchoalveolar lavage. As a rule, the effectiveness of treatment is assessed after 6-12 weeks, after the start of therapy, and, according to these results, it is possible to estimate the likelihood of cure and the patient's life expectancy. The most favorable prognosis is in those patients who have achieved complete remission. This group includes all patients whose life expectancy exceeds 3 years. If the tumor has decreased by 50%, while there is no metastasis, it is possible to speak of partial remission. Life expectancy is correspondingly less than in the first group. With a tumor that does not respond to treatment and active progression, the prognosis is poor.

After conducting a statistical study, the effectiveness of chemotherapy was revealed and it is about 70%, while in 20% of cases, complete remission is achieved, which gives survival rates close to those of patients with a localized form.

Limited stage

At this stage, the tumor is located within one lung, and nearby lymph nodes may also be involved.

The applied methods of treatment:

combined: chemotherapy + radiation therapy followed by prophylactic cranial irradiation (PCR) in remission;
chemotherapy with or without PCO, for patients with impaired respiratory function;
surgical resection with adjuvant therapy for stage 1 patients;
the combined use of chemotherapy and thoracic radiation therapy is the standard approach for patients with limited stage, small cell lung cancer.

According to statistics from clinical trials, combination treatment compared with chemotherapy without radiation therapy increases the 3-year prognosis of survival by 5%. The drugs used are platinum and etoposide. The prognostic indicators for life expectancy are 20-26 months and the prognosis for 2-year survival is 50%.

Ineffective ways to increase your forecast:

increasing the dose of drugs;
the action of additional types of chemotherapy drugs.

The duration of the chemotherapy course has not been determined, but, nevertheless, the duration of the course should not exceed 6 months.

The question of radiation therapy: Many studies show its benefits in the 1-2 cycle of chemotherapy. The duration of the course of radiation therapy should not exceed 30-40 days.

maybe application of standard radiation courses:

Once a day for 5 weeks;
2 or more times a day for 3 weeks.

Hyperfractionated thoracic radiation therapy is considered preferred and contributes to a better prognosis.

Patients of an older age (65-70 years) tolerate treatment significantly worse, the prognosis of treatment is much worse, since they react poorly to radiochemotherapy, which in turn manifests itself in low efficiency and large complications. Currently, the optimal therapeutic approach for elderly patients with small cell cancer has not been developed.

Patients who have achieved remission of the tumor process are candidates for prophylactic cranial irradiation (PCR). Research results indicate a significant reduction in the risk of metastases in the brain, which is 60% without the use of PCO. PCO improves the prognosis of 3-year survival from 15% to 21%. Often, survivors have impairments in neurophysiologic function, but these impairments are not associated with the passage of POC.

Extensive stage

The spread of the tumor occurs outside of the lung in which it originally appeared.

Standard therapies:

combined chemotherapy with or without prophylactic cranial radiation;

Note! The use of higher doses of chemotherapy drugs remains an open question.

For a limited stage, in the case of a positive response to chemotherapy, an extensive stage of small cell lung cancer, prophylactic cranial radiation is indicated. The risk of metastases in the central nervous system within 1 year is reduced from 40% to 15%. There was no significant deterioration in health after PCO.

Combined radiochemotherapy does not improve the prognosis compared to chemotherapy, however, thoracic radiation is advisable for palliative therapy of distant metastases.

Patients diagnosed with advanced stage have deteriorated health conditions that complicate aggressive therapy. The conducted clinical studies did not reveal an improvement in the prognosis of survival with a decrease in doses of drugs or with a transition to monotherapy, but, nevertheless, the intensity in this case should be calculated from the individual assessment of the patient's health.

Disease prognosis

As mentioned earlier, small cell lung cancer is one of the most aggressive forms of all. What is the prognosis of the disease and how long the patients live depends directly on the treatment of oncology in the lungs. Much depends on the stage of the disease, and what type it belongs to. There are two main types of lung cancer - small cell and non-small cell.

Smokers are susceptible to small cell lung cancer; it is less common, but spreads very quickly, forming metastases and invading other organs. It is more sensitive to chemical and radiation therapy.

Life expectancy in the absence of appropriate treatment ranges from 6 to 18 weeks, but the survival rate reaches 50%. With appropriate therapy, life expectancy increases from 5 to 6 months. The worst prognosis is in patients with a 5-year illness. About 5-10% of patients survive.

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Long-term treatment results small cell lung cancer (MPL) remain unsatisfactory (Table 10), although, according to some data, they have improved over the previous decade.

Over the past 20 years, as a result of the introduction of combined methods of treatment, in particular, combined chemotherapy (XT), there is an improvement in survival rates with an increase in 5-year survival from 5.2% in 1972-1981. to 12.2% in 1982-1996, the median survival during the same period increased from 11.8 to 18.8 months (9th World Conference on Lung Cancer, Japan, Tokyo, 2000).

Table 10. Long-term results of SCLC treatment

One of the main treatments is XT using combined regimens. The surgical method is used at an early stage of the process (localized process). The importance of the surgical method in the early stages is confirmed by the study of the morphological variant of the malignancy of the process and the clarification of the lesion of the mediastinal lymph nodes.

Radiation therapy is also a mandatory component of the treatment of a localized process. When complete regression (PR) can be used prophylactic brain irradiation (PRI).

Localized small cell lung cancer

At stage I of the disease, surgical treatment is used, followed by XT or chemotherapy with radiation of the chest. Standard XT mode, as with non-small cell lung cancer (NSCLC), is the mode:

Cisplatin IV 75-100 mg / m2 1 r / day on the 1st day against the background of overhydration and antiemetics
+
Etoposide IV drip 80-100 mg / m2 1 r / day in 1, 2 and 34 days
Every 3 weeks

In a localized process, it is used in combination with radiation therapy in a total dose of 40-45 Gy, which must be performed during the 1st or 2nd cycle.

In such patients and patients with complete remission after chemotherapy, foreign authors use POHM. Patients with small cell lung cancer (MPL) should undergo a thorough, sometimes invasive examination to determine the stage of the disease. The results of surgical treatment of localized SCLC make it possible to achieve good results with a 2-year survival rate.

In stage II localized SCLC, surgery results in satisfactory local control after induction CT with radiation therapy. The presence of N2 is generally a contraindication to surgical treatment.

However, in case of localized small cell lung cancer with stage IIIA PR after cytoreductive CT, it is possible to include surgery and then chemotherapy in the treatment plan. radiation therapy (RT)... The best prognostic factor is the absence of residual tumor in the removed specimen.

According to Shepherd F.A. (2002), the 5-year survival rate of all operated patients is 25-35%:

Surgery (of all patients with SCLC) - 5%;

undergo surgery after induction XT with MCLC - 75%:

Of these, 8-100% are radically operated on (on average 50%);
- of them histological complete regression - 0-37%;

5-year survival rate in all operated patients is 25-35%:

5-year survival rate for stage I small cell lung cancer -\u003e 50%;
- 5-year survival rate after XT and RT - 20-25%.

Similar results were obtained using alternating EC and CAV + LT at a dose of 45 Gy.

The following modeschemotherapy can be used for MRI:

Treatment modes	Drugs (i / v, drip), mg / m2	Interval, weeks
EP	Cisplatin 80 on the 1st day + etoposide 120 on the 1,2, 3rd days	3
CAE	Cyclophosphamide 1000 on day 1 + doxorubicin 45 on day 1 + etoposide 100 on days 1, 2, 3 or 1, 3, 5	3
CAV	Cyclophosphamide 1000 on the 1st day + Doxorubicin 50 on the 1st day + Vincoistin 1.4 on the 1st day	3
VICE	Vincristine 1.4 on the 1st day + Ifosfamide 5000 on the 1st day + Carboplatin 300 on the 1st day + etoposide 180 on the 1st and 2nd days	3
CDE	Cyclophosphamide 1000 on the 1st day + doxorubicin 45 on the 1st day + etoposil 100 in 1.3. 5th day	3
CAM	Cyclophosphamide 1000-1500 on the 1st day + doxorubicin 60 on the 1st day + methotoexagt 30 on the 1st day	3
AVP	Nimustine 3-2 mg / kg on the 1st day + etoposide 100 on the 4th, 5th, 6th days + cisplatin 40 on the 2nd. 8th days	4-6
TEP	Paclitaxel 175 on day 1 + etoposide 100 on days 1, 2, 3 + cisplatin 75 on day 1	3-4

Use of intensive XT regimens with increasing doses included in the regimens medicines (drugs), as a rule, leads to an improvement in the immediate results of treatment. However, even with such a tumor sensitive to XT as SCLC, the advantage of high-dose regimens has not been proven.

The optimal duration of chemotherapy for patients with localized small cell lung cancer has not been fully specified, however, with an increase in the duration of treatment from 3 to 6 months, there was no improvement in survival.

The risk of developing metastases in the central nervous system can be reduced by more than 50% by irradiation of the central nervous system at a dose of 24 Gy.

When using chemoradiation treatment, the hyperfractionation regimen is preferable:

Advanced small cell lung cancer

With advanced SCLC, the median survival rate is 6-12 months, and the 5-year survival rate is 2.3%. Combination chemotherapy plus radiation therapy does not improve survival when compared to chemotherapy alone. However, radiation therapy is important in the palliative treatment of symptoms of both primary tumor and metastases, especially in the brain, meninges, bones.

A meta-analysis of 7 randomized trials showed the importance of CNS irradiation in patients with PD - a decrease in relapses in the central nervous system, an improvement in relapse-free and overall survival was reported: 3-year survival increased from 15 to 21%.

The following combination XT modes provide similar survival rates:

CAV (cyclophosphamide + doxorubicin + vincristine);
CAE (cyclophosphamide + doxorubicin + etoposide);
EP (etoposide + cisplatin);
EC (etoposide + carboplatin);
CAM (cyclophosphamide + doxorubicin + ethotrexate);
ICE (Ifosfamide + Carboplatin + Etoposide);
CEV (cyclophosphamide + etoposide + vincristine);
PET (cisplatin + etoposide + paclitaxel);
CAEV (cyclophosphamide + doxorubicin + etoposide + vincristine).

The highest efficiency (64.7%) in relation to various visceral metastases is possessed by the regimen with nimustine - AVP, which turned out to be more effective in relation to metastases in the central nervous system compared to other regimens.

For brain metastases, radiation therapy, XT, and chemoradiation are used:

Of particular interest is the use of new drugs in previously untreated patients with advanced SCLC (Table 11).

Table 11. Efficacy of new drugs in previously untreated patients with advanced small cell lung cancer

New drugs are also being studied in combination chemotherapy regimens.

They include 2- and 3-component treatment regimens, as well as combinations with radiation therapy:

Treatment modes	Drugs (i / v, drip), mg / m2	Interval, weeks	Effect
	Docetaxel 100 1 h		23% CR
	Paclitaxel 250 24 h + G-CSF		53% OE
TS	Paclitaxel 175 on Day 1 + Carboplatin 400 on Day 1	3-4
TP	Docetaxel 75 on Day 1 + Cisplatin 75 on Day 1	3-4
TG	Paclitaxel 175 on day 1 + gemcitabine 1000 on days 1, 8, 15	4
TEP	Paclitaxel 175 3 h + cisplatin 80 + etoposide 80 IV on day 1, 160 orally on days 2-3 + G-CSF		83% RE 22% complete regression
TEP	Paclitaxel 135 on day 1 + cisplatin 75 on day 1 + etoposide 80 on days 1-3		90% MA MB - 47 weeks
GEP	Gemcitabine 800 on days 1, 8 + etoposide 50 on days 1-5 + cisplatin 75 on day 1		54% MA 75% - untreated patients
IP	Irinotecan 60 on the 1st, 8th, 15th days + cisplatin 50 on the 1st day + radiation therapy 4 weeks		83% MA, 30% PR, MB 14.3 months - LP 86% MA, 29% PR, MB 13 months - RP
CN	Carboplatin 300 + Vinorelbine 25 on the 1st, 8th days x 6 cycles		74% OE MB - 9 months

CR - partial emission, LP - localized process, ERP - common process

Selected results of comparing the effectiveness of the modes:

With a comparable effectiveness of the EP and TEP regimens (MB, respectively, 9.84 months and 10.33 months), the toxicity of the 2nd regime was higher;
the study of the TP regimen as the 1st line of XT of advanced SCLC in previously untreated patients showed its effectiveness in 59% of patients;
the data of the JCOG-9511 study (Japan) on the advantages of the IP mode in comparison with the standard EP scheme were obtained: MB, respectively, 9.4 and 12.8; MA, respectively, 83 and 68%.

In order to clarify the results, additional studies are currently being carried out. In the treatment of SCLC, as in NSCLC, all new directions of drug treatment are being investigated, with one main trend - from nonspecific antiproliferative drugs to targeted or referred to by foreign authors as "targeted" therapy aimed at certain genes, receptors, proteins, and etc.

V.A. Gorbunova, A.F. Marenich, 3.P. Mikhina, O. V. Izvekova