Home Removal How is small cell lung cancer treated? Modern therapeutic tactics for small cell lung cancer (SCLC)

Removal

How is small cell lung cancer treated? Modern therapeutic tactics for small cell lung cancer (SCLC)

One of the most common and difficult-to-treat diseases among men is small cell lung cancer. At the initial stage, the disease is quite difficult to recognize, but with timely treatment, the chances of a favorable outcome are high.

Small cell lung cancer is one of the most malignant tumors according to histological classification, which is very aggressive and gives extensive metastases. This form of cancer accounts for about 25% of other types of lung cancer and, if not detected early and treated properly, is fatal.

For the most part, this disease affects men, but recently there has been an increase in incidence among women. Due to the absence of signs of the disease in the early stages, as well as the rapid growth of the tumor and the spread of metastases, in most patients the disease takes an advanced form and is difficult to cure.

All information on the site is for informational purposes only and is NOT a guide to action!
Can give you an ACCURATE DIAGNOSIS only DOCTOR!
We kindly ask you NOT to self-medicate, but make an appointment with a specialist!
Health to you and your loved ones! Do not give up

Causes

Smoking- the first and the most main reason lung cancer. The age of the person who smokes, the number of cigarettes per day and the duration of the habit affect the likelihood of developing small cell lung cancer.

A good prevention is to give up cigarettes, which will significantly reduce the possibility of disease, however, a person who has ever smoked will always be at risk.

Statistically, smokers develop lung cancer 16 times more often than non-smokers, and lung cancer is diagnosed 32 times more often in those who started smoking in adolescence.

Nicotine addiction is not the only factor that can trigger the disease, so there is a possibility that smoking people may also be among the patients with lung cancer.

Heredity– the second most important reason that increases the risk of disease. The presence of a special gene in the blood increases the likelihood of developing small cell lung cancer, so there are fears that those people whose relatives suffered from this type of cancer may also get sick.

Ecology– a reason that has a significant impact on the development of lung cancer. Exhaust gases and industrial waste poison the air and, along with it, enter the human lungs. Also at risk are people who have frequent contact with nickel, asbestos, arsenic or chromium due to their professional activities.

Severe lung diseases– prerequisites for the development of lung cancer. If a person has had tuberculosis or chronic obstructive pulmonary disease throughout his life, this may cause the development of lung cancer.

Symptoms

Lung cancer, like most other organs, at the initial stage does not bother the patient and does not have a pronounced severe symptoms. It can be noticed with timely fluorography.

Depending on the stage of the disease, the following symptoms are distinguished:

the most common symptom is a persistent cough. However, it is not the only accurate sign, since people who smoke (namely, they malignant tumor diagnosed more often than in non-smokers), chronic cough is observed even before illness. For more late stage cancer, the nature of the cough changes: it intensifies, is accompanied by pain and expectoration of bloody fluid
with small cell lung cancer a person often experiences shortness of breath, which is associated with difficulty in the flow of air through the bronchi, which disrupts the proper functioning of the lung;
at stages 2 and 3 the disease is not uncommon sudden fevers or periodic fever. Pneumonia, which often affects smokers, can also be one of the signs of lung cancer;
systematic chest pain when coughing or trying to breathe deeply;
The greatest danger is posed by pulmonary bleeding, which is caused by tumor growth into the pulmonary vessels. This symptom indicates the neglect of the disease;
when the tumor increases in size, it can depress neighboring organs, which can result in pain in the shoulders and limbs, swelling of the face and hands, difficulty swallowing, hoarseness in the voice, prolonged hiccups;
in the advanced stage of cancer, the tumor seriously affects other organs, which further worsens the unfavorable picture. Metastases that reach the liver can cause jaundice, pain under the ribs, metastases to the brain lead to paralysis, loss of consciousness and disorders of the speech center of the brain, metastases to the bones cause pain and aches in them;

All of the above symptoms may be accompanied by sudden weight loss, loss of appetite, chronic weakness and fatigue.

Based on how intense the symptoms manifest themselves and how promptly a person seeks help from a doctor, we can make a forecast about the chances of his recovery.

Diagnostics

Adults, especially those who smoke, should be periodically screened for lung cancer.

Diagnosis of a tumor in the lung consists of the following procedures:

Fluorography to detect any changes in the lungs. This procedure is carried out when medical examination, after which the doctor prescribes other examinations that will help in making the correct diagnosis.
Clinical and biochemical analysis blood.
Bronchoscopy is a diagnostic method that examines the extent of lung damage.
Biopsy – removal of a tumor sample surgically to determine the type of tumor.
Radiation diagnostics, which includes X-ray examination, magnetic resonance imaging (MRI) and positive emission tomography (PET), which help determine the location of tumor foci and clarify the stage of the disease.

Video: About early diagnosis lung cancer

Treatment

Treatment tactics for small cell lung cancer are developed based on the clinical picture of the disease and the general well-being of the patient.

There are three main methods of treating lung cancer, which are often used in combination:

surgical removal of the tumor;
radiation therapy;
chemotherapy.

Surgical removal of the tumor makes sense at an early stage of the disease. Its purpose is to remove the tumor or part of the affected lung. This method is not always possible with small cell lung cancer due to its rapid development and late detection, therefore more radical methods are used for its treatment.

The possibility of surgery is also excluded if the tumor affects the trachea or neighboring organs. In such cases, chemotherapy and radiation therapy are immediately resorted to.

Chemotherapy for small cell lung cancer can give good results if used in a timely manner. Its essence lies in taking special medications that destroy tumor cells or significantly slow down their growth and reproduction.

The patient is prescribed the following medications:

"Bleomycin";
"Methotrexate";
"Vinorelbine";
Vincristine, etc.

The drugs are taken at intervals of 3-6 weeks and at least 7 courses must be completed to achieve remission. Chemotherapy helps shrink tumors, but cannot guarantee full recovery. However, it can prolong a person’s life even at the fourth stage of the disease.

Radiation therapy or radiotherapy is a method of treating cancer using gamma radiation or x-rays to kill or slow the growth of cancer cells.

It is used for inoperable lung tumors, when the tumor affects the lymph nodes, or when surgery is not possible due to the patient’s unstable condition (for example, serious illness other internal organs).

During radiation therapy, the affected lung and all areas of metastasis are irradiated. For greater effectiveness, radiation therapy is combined with chemotherapy if the patient is able to tolerate it combination treatment.

One of possible options Providing care to a patient with lung cancer is palliative treatment. It is applicable when everything possible methods stopping the development of the tumor did not yield any results, or when lung cancer was detected at the most advanced stage.

Palliative care is designed to relieve last days the patient, providing him with psychological assistance and pain relief severe symptoms cancer. Methods of such treatment depend on the person’s condition and are purely individual for each person.

There are various traditional methods treatments for small cell lung cancer, which are popular in narrow circles. Under no circumstances should you rely on them and self-medicate.

Every minute is important for a successful outcome, and often people waste precious time in vain. At the slightest sign of lung cancer, you should immediately consult a doctor, otherwise death is inevitable.

The choice of treatment method for a patient is an important stage on which his future life depends. This method should take into account the stage of the disease and the psycho-physical condition of the patient.

You can learn more about the treatment methods for peripheral lung cancer.

How long do people live (life expectancy) with small cell lung cancer?

Despite the transient course of small cell lung cancer, it is more sensitive to chemotherapy and radiotherapy compared to other forms of cancer, so with timely treatment the prognosis can be favorable.

The most favorable outcome is observed when cancer is detected at stages 1 and 2. Patients who start treatment on time manage to achieve complete remission. Their life expectancy already exceeds three years and the number of people cured is about 80%.

At stages 3 and 4, the prognosis worsens significantly. With complex treatment, the patient's life can be extended by 4-5 years, and the percentage of survivors is only 10%. If left untreated, the patient dies within 2 years from the date of diagnosis.

Lung cancer is one of the most common oncological diseases, which is very difficult to cure, but there are many ways to prevent its occurrence. First of all, it is necessary to cope with nicotine addiction, avoid contact with harmful substances and undergo regular medical examinations.

Timely detection of small cell lung cancer in the early stages significantly increases the chances of defeating the disease.

Cancer is a malignant neoplasm that destroys healthy cells of the body as a result of mutation. According to the International Agency for Research on Cancer, its most common location is the lungs.

According to its morphology, lung cancer is divided into non-small cell (including adenocarcinoma, squamous cell, large cell, mixed) - about 80-85% of the total incidence, and small cell - 15-20%. Currently, there is a theory of the development of small cell lung cancer as a result of degeneration of the cells of the epithelial lining of the bronchi.

Small cell lung cancer is the most aggressive, characterized by early metastasis, latent course and the most unfavorable prognosis, even in case of treatment. Small cell lung cancer is the most difficult to treat, ending in death in 85% of cases.

The early stages are asymptomatic and are more often detected by chance during routine examinations or when visiting a clinic with other problems.

Symptoms may indicate the need for testing. The appearance of symptoms in the case of SCLC may indicate an already advanced stage of lung cancer.

Reasons for development

Small cell lung cancer is directly related to smoking. Long-time smokers are 23 times more likely to develop lung cancer than non-smokers. 95% of people with small cell lung carcinoma are men over 40 who smoke.
Inhalation of carcinogenic substances - working in “harmful” industries;
Unfavorable environmental conditions;
Frequent or chronic diseases lungs;
Burdened heredity.

No smoking - best prevention small cell lung cancer.

Symptoms of lung cancer

Cough;
Dyspnea;
Noisy breathing;
Finger deformity “drum sticks”;
Dermatitis;
Hemoptysis;
Weight loss;
Symptoms of general intoxication;
Temperature;
In the 4th stage - obstructive pneumonia, secondary symptoms appear from the affected organs: bone pain, headaches, confused consciousness.

Signs of pathology may differ depending on the location of the original neoplasm.

Small cell cancer is often central, less often peripheral. Moreover, the primary tumor is rarely detected radiographically.

Diagnostics

When identifying primary signs pathologies on fluorography and according to clinical indications (smoking, heredity, age over 40 years, gender and others), more informative diagnostic methods recommended in pulmonology are used. Main diagnostic methods:

Tumor imaging by radiation methods: radiography, computed tomography (CT), positron emission tomography (PET-CT).
Determination of tumor morphology (i.e. its cellular identification). To conduct a histological (cytological) analysis, a puncture is taken using bronchoscopy (which is also a non-radiation imaging method), and other methods of obtaining material.

Stages of SCLC

The tumor is less than 3 cm in size (measured in the direction of maximum elongation) and is located in one segment.
Less than 6 cm, not extending beyond one segment of the lung (bronchus), single metastases in nearby lymph nodes
More than 6 cm, affects the nearest lobes of the lung, the adjacent bronchus, or the outlet into the main bronchus. Metastases spread to distant lymph nodes.
Cancer neoplasia can spread beyond the lungs, with growth into neighboring organs, multiple distant metastasis.

International classification TNM

Where T is the state indicator primary tumor, N – regional lymph nodes, M – distant metastasis

T x – the data is insufficient to assess the condition of the tumor, or it has not been identified,

T 0 – the tumor is not detected,

T IS – non-invasive cancer

and from T 1 to T 4 – stages tumor growth from: less than 3 cm, to a size where size does not matter; and stages of location: from local in one lobe to capture pulmonary artery, mediastinum, heart, carinae, i.e. before growing into neighboring organs.

N – indicator of the condition of regional lymph nodes:

N x – the data is insufficient to assess their condition,

N 0 – no metastatic lesion was detected,

N 1 – N 3— characterize the degree of damage: from the closest lymph nodes to those located on the side opposite the tumor.

M – state of distant metastasis:

M x – there is insufficient data to determine distant metastases,

M 0 – no distant metastases were found,

M 1 – M 3 – dynamics: from the presence of signs of a single metastasis to expansion beyond the chest cavity.

More than 2/3 of patients are diagnosed III-IV stage, therefore, SCLC continues to be considered according to the criteria of two significant categories: localized or widespread.

Treatment

If this diagnosis is made, treatment for small cell lung cancer directly depends on the degree of damage to the organs of a particular patient, taking into account his medical history.

Chemotherapy in oncology is used to form the boundaries of the tumor (before its removal), in postoperative period to destroy possible cancer cells and as the main part healing process. It should reduce the tumor, radiation therapy should consolidate the result.

Radiation therapy is ionizing radiation that kills cancer cells. Modern devices generate highly targeted beams that minimally damage nearby areas of healthy tissue.

Necessity and consistency surgical methods and therapeutic ones are determined directly by the attending oncologist. The goal of therapy is to achieve remission, preferably complete.

Treatment procedures - early stages

Surgical surgery- unfortunately, the only option today for removing cancer cells. The method is used at stages I and II: removal of the entire lung, lobe or part thereof. Postoperative chemotherapy is a mandatory component of treatment, usually with radiation therapy. In contrast to non-small cell lung cancer, in the initial stage of which it is possible to limit oneself to tumor removal. Even in this case, the 5-year survival rate does not exceed 40%.

The chemotherapy regimen is prescribed by an oncologist (chemotherapist) - medications, their dosages, duration and quantity. Assessing their effectiveness and based on the patient’s well-being, the doctor can adjust the course of treatment. As a rule, additional antiemetic drugs are prescribed. Various alternative treatments, dietary supplements, including vitamins, can worsen your condition. It is necessary to discuss their use with your oncologist, as well as any significant changes in your health.

Treatment procedures - stages 3 and 4

The usual regimen for localized forms of more complex cases is combination therapy: polychemotherapy (poly means the use of not one, but a combination of drugs) - 2-4 courses, preferably in combination with radiation therapy for the primary tumor. When remission is achieved, prophylactic irradiation of the brain is possible. This therapy increases life expectancy to an average of 2 years.

For the common form: polychemotherapy 4-6 courses, radiation therapy - according to indications.

In cases where tumor growth has stopped, it is referred to as partial remission.

Small cell lung cancer responds very well to chemotherapy, radiotherapy and radiation therapy. The insidiousness of this oncology is that there is a high probability of relapses, which are no longer sensitive to such antitumor procedures. Possible course of relapse is 3-4 months.

Metastasis occurs (cancer cells are transferred through the bloodstream) to organs that are most intensively supplied with blood. The brain, liver, kidneys, and adrenal glands are affected. Metastases penetrate the bones, which also leads to pathological fractures and disability.

If the above treatment methods are ineffective or impossible to use (due to age and individual characteristics patient) palliative treatment is carried out. It is aimed at improving the quality of life, mainly symptomatic, including pain relief.

How long do people live with SCLC?

Your life expectancy depends on the stage of the disease, your general health and the treatment methods used. According to some data, women have better sensitivity to treatment.

A transient disease can give you from 8 to 16 weeks, in case of insensitivity to therapy or refusal of it.

The treatment methods used are far from perfect, but it increases your chances.

In the case of combined treatment in stages I and II, the probability of 5-year survival (after five years complete remission is said) is 40%.

At more serious stages, life expectancy with combination therapy increases by an average of 2 years.

In patients with a localized tumor (i.e. not an early stage, but without distant metastasis) using complex therapy, 2-year survival is 65-75%, 5-year survival is possible in 5-10%, with good condition health - up to 25%.

In the case of advanced SCLC - stage 4, survival up to a year. The forecast is complete cure in this case: cases without relapse are extremely rare.

Afterword

Someone will look for the causes of cancer without understanding why they need it.

Believers tolerate illness more easily, perceiving it as a punishment or test. Perhaps this will make them feel better, and may this bring peace and fortitude in the struggle for life.

A positive attitude is necessary for favorable outcome treatment. Just how to find the strength to resist pain and remain yourself. It is impossible to give the right advice to a person who has heard a terrible diagnosis, nor to understand it. It’s good if your family and friends help you.

(No ratings yet)

Small cell pulmonary oncology is considered a fairly common disease among men. This form is quite difficult to determine in the initial stages, but if it is detected in time and treatment is started, then the patient has every chance of a favorable prognosis.

Small cell lung cancer is characterized by increased malignancy, an aggressive course and a tendency to extensive metastasis. Therefore, if you do not identify it in the early stages of progression and do not start timely treatment, then the patient will die. This type of cancer accounts for a quarter of cases of the total number of pulmonary pathologies.

Concept of disease

So, small cell lung cancer is a malignant tumor formation that is prone to rapid progression and extensive development.

This kind of oncology has a hidden, asymptomatic onset, so it often happens that patients end up in the hands of specialists when the disease is already in an advanced stage.

More often, pathology is found in patients of the stronger sex, although in last years the disease began to affect the fair half, which is most likely due to its spread among women.

Types

Small cell pulmonary oncology is divided into two pathological forms:

Small cell carcinoma– this is a rather unfavorable oncological process, which is characterized by rapid and aggressive development with extensive metastases, therefore the only treatment option is combined polychemotherapy;
Combined small cell cancer– this type of oncology is characterized by the presence of signs of adenocarcinoma in combination with symptoms of squamous cell and oat cell carcinoma.

Causes

The main cause of pulmonary small cell oncology is. The degree of risk of developing such a pathology is largely determined by age characteristics the patient, the number of cigarettes smoked during the day, smoking experience, etc.

The presence of nicotine addiction increases the likelihood of oncological processes in the lung tissues by 16-25 times. In addition to smoking, the following factors can cause cancer:

Pulmonary pathologies such as obstruction, tuberculosis, etc.;
Unfavorable environmental conditions;
Hereditary predisposition;
Work in production with increased harmfulness.

Exposure to radiation can also become a trigger for the occurrence of cancerous tumor in the lungs.

Symptoms

As previously reported, the pathology rarely manifests itself in the initial stages of development, therefore it is detected at the stage of active progression, accompanied by the following symptomatic manifestations:

The occurrence of an unexplained cough that gradually worsens and cannot be treated;
Refusal to eat, weight loss;
Tendency to frequent pulmonary pathologies such as pneumonia or bronchitis;
Excessive fatigue and fatigue, shortness of breath;
Chest pain that tends to increase in intensity when laughing, coughing or deep breathing;
Sudden rises in temperature, up to a feverish state;
Over time, with a cough, mucous sputum of a rusty brown or red color begins to be released, hemoptysis;
Extraneous whistling sounds when breathing.

Unusual signs of lung cancer are described in this video:

With extensive growth of the tumor, additional symptoms such as ossalgia, jaundice, neurological manifestations, swelling of the supraclavicular and cervical lymph node structures occur.

The large size of the formation has a depressing effect on neighboring systems, causing additional pain, puffiness of the face, problems with swallowing, difficult to eliminate hiccups, etc.

Stages and prognosis for small cell lung cancer

Small cell forms of lung cancer develop according to the following scenario:

Stage 1 – oncology is localized, the formation is located only in one part of the chest and the regional lymph node system. At this stage, the disease responds positively to radiation if its volume and intensity are selected correctly;
Stage 2 is manifested by generalization of the tumor process, which spreads beyond one chest half and regional lymph nodes, growing throughout the body. In this case, the prognosis is often unfavorable.

Diagnosis

The diagnostic process is based on several research procedures:

Fluorographic examination;
Bronchoscopic procedure;
tumors;
X-ray examination;
or MRI, diagnosis.

Principles of treatment

It is recommended to combine such treatment with a treatment that involves irradiation of primary tumor foci and lymph node structures. A combined approach to the treatment of small cell lung cancer helps prolong the life of a cancer patient by 2 years.

If the small cell tumor is widespread, then at least 5-6 chemotherapy courses are indicated. If metastases have penetrated the bone, brain, and adrenal structures, then treatment with radiation is resorted to.

Although small cell lung cancer is different hypersensitivity to polychemotherapy and radiation exposure, the likelihood of relapse is quite high.

Patient life expectancy

Without proper treatment, lung cancer is 100% fatal.

Predicting the life expectancy of patients with small cell lung cancer depends on the development of the oncological process and the correctness of its therapy.

If small cell lung cancer is detected first by pathology, then the number of survivors over a five-year period will be about 21-38%. When detected in advanced stages 3.4, survival rate is a maximum of 9%.

If during treatment there is a tendency towards a decrease in tumor parameters, then oncologists regard this phenomenon as a favorable sign, because the patient has a good chance of a long life - with a partial remission result, the survival rate will be about 50%, with a complete remission - 70-90%.

Disease Prevention

An excellent measure to prevent lung cancer is to get rid of nicotine addiction, and passive smoking should also be avoided. Equally important is the prevention of pulmonary pathologies and general infections.

It is necessary to include gymnastics, morning exercises, fitness or jogging in your daily routine. Such a measure will have a beneficial effect on the pulmonary system and will help control your weight.

If you have harmful addictions such as using or it is recommended to get rid of them. If the profession is associated with high-hazard production, then you need to follow safety precautions and use personal protective equipment.

Once a year you need to undergo preventive fluorography, which will help to timely detect oncological processes in the lungs, if any.

Video scientific-practical conference about small cell lung cancer:

In the structure of oncological diseases, lung cancer is one of the most common pathologies. It is based on malignant degeneration of the epithelium lung tissue, air exchange disturbance. The disease is characterized by high mortality. The main risk group consists of smoking men 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 cancer 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 tumors like systemic disease, in the early stages of which, are almost always present in the regional lymph nodes. , suffer from this type of tumor most often, but the percentage of cases is growing significantly. Almost all patients wear enough severe form cancer, this is associated with rapid growth tumors and widespread metastasis.

Small cell lung cancer

Causes of small cell lung cancer

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

smoking;
radon exposure;
pulmonary asbestosis;
viral infection;
dust exposure.

Clinical manifestations of small cell lung cancer

Symptoms of small cell lung cancer:

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

Grades of small cell lung cancer

Stage 1 - the tumor size is 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, causing atelectasis;
Stage 3 - the tumor rapidly spreads to neighboring organs, its size has increased from 6 to 7 cm, and 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 human body and causes symptoms such as:

headache;
hoarseness or loss of voice altogether;
general malaise;
loss of appetite and a sharp decline in weight;
back pain, etc.

Diagnosis of small cell lung cancer

Despite all the clinical examinations, history taking and listening to the lungs, quality is also necessary, which is carried out using methods such as:

skeletal scintigraphy;
chest x-ray;
expanded, clinical analysis blood;
computed tomography (CT);
liver function tests;
magnetic resonance imaging (MRI)
positron emission tomography (PET);
sputum analysis ( cytological examination for the purpose of detecting cancer cells);
thoracentesis (sampling of fluid from the chest cavity around the lungs);
– the most common method for diagnosing malignant neoplasms. 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 perform a biopsy:

bronchoscopy in combination with biopsy;
carried out using CT;
endoscopic ultrasonography with biopsy;
mediastinoscopy in combination with biopsy;
open lung biopsy;
pleural biopsy;
videothoracoscopy.

Treatment of small cell lung cancer

Chemotherapy occupies the most important place in the treatment of small cell. Without appropriate treatment for lung cancer, the patient dies 5-18 weeks after diagnosis. Polychemotherapy helps to increase the mortality rate to 45–70 weeks. It is used both as an independent method of therapy and in combination with surgical intervention or radiation therapy.

Purpose 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 6-12 weeks after the start of therapy, and based on these results, the likelihood of cure and the patient’s life expectancy can be assessed. The most favorable prognosis is for those patients who achieve complete remission. This group includes all patients whose life expectancy exceeds 3 years. If the tumor has decreased by 50%, and there is no metastasis, it is possible to talk about partial remission. Life expectancy is correspondingly shorter than in the first group. For tumors that cannot be treated and are actively progressing, the prognosis is poor.

After a statistical study, the effectiveness of chemotherapy was revealed and 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.

Treatment methods used:

combined: chemo+radiation therapy followed by prophylactic cranial irradiation (PCR) during remission;
chemotherapy with or without PCO, for patients who have deteriorating respiratory function;
surgical resection with adjuvant therapy for patients with stage 1;
The combined use of chemotherapy and thoracic radiotherapy is the standard approach for patients with limited-stage, small cell LC.

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

Ineffective ways to increase your forecast:

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

The duration of the chemotherapy course is not defined, but, nevertheless, the duration of the course should not exceed 6 months.

Question about radiation therapy: Many studies show its benefits during 1-2 cycles of chemotherapy. The duration of the course of radiation therapy should not exceed 30-40 days.

Maybeapplication standard courses irradiation:

1 time per day for 5 weeks;
2 or more times a day for 3 weeks.

Hyperfractionated thoracic radiotherapy is considered preferable and results in a better prognosis.

Older patients (65-70 years old) tolerate treatment much worse; the treatment prognosis is much worse, since they respond rather poorly to radiochemotherapy, which in turn manifests itself in low effectiveness and major 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 experience impairments in neurophysiological function, but these impairments are not associated with undergoing PCO.

Extensive stage

The tumor spreads beyond the lung in which it originally appeared.

Standard therapy methods:

combination chemotherapy with or without prophylactic cranial irradiation;

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

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

Combined radiochemotherapy does not improve the prognosis compared to chemotherapy, but thoracic irradiation is advisable for palliative treatment of distant metastases.

Patients diagnosed with an advanced stage have a deteriorating health status, which complicates aggressive therapy. Clinical studies have not revealed an improvement in survival prognosis when reducing drug doses or switching to monotherapy, but, nevertheless, the intensity in this case should be calculated from an individual assessment of the patient’s health status.

Disease prognosis

As mentioned earlier, small cell lung cancer is one of the most aggressive forms everyone The prognosis of the disease and how long patients live depends directly on the treatment of lung cancer. A lot depends on the stage of the disease and what type it is. There are two main types of lung cancer - small cell and non-small cell.

Small cell lung cancer affects smokers; it is less common, but spreads very quickly, forming metastases and affecting 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, and the survival rate reaches 50%. With the use of appropriate therapy, life expectancy increases from 5 to 6 months. The worst prognosis is for patients with a 5-year illness period. Approximately 5-10% of patients remain alive.

Informative video

(Moscow, 2003)

N. I. Perevodchikova, M. B. Bychkov.

Small cell lung cancer (SCLC) is a unique form of lung cancer, significantly different in its biological characteristics from other forms collectively referred to as non-small cell lung cancer (NSCLC).

There is strong evidence that the occurrence of SCLC is associated with smoking. This is confirmed by the changing frequency of this form of cancer.

An analysis of 20 years of SEER data (1978-1998) showed that, despite the annual increase in the number of patients with lung cancer, the percentage of patients with SCLC decreased from 17.4% in 1981 to 13.8% in 1998, which, according to -apparently associated with the intensive fight against smoking in the United States. Noteworthy is the relative, compared to 1978, reduction in the risk of death from SCLC, first registered in 1989. In subsequent years, this trend continued, and in 1997, the risk of death from SCLC corresponded to 0.92 (95% Cl 0.89 - 0.95,<0,0001) по отношению к риску смерти в 1978 г., принятому за единицу. Эти достаточно скромные, но стойкие результаты отражают реальное улучшение результатов лечения больных МРЛ -крайне злокачественной, быстро растущей опухоли, без лечения приводящей к смерти в течение 2-4 месяцев с момента установления диагноза.

The biological features of SCLC determine the rapid growth and early generalization of the tumor, which at the same time has a high sensitivity to cytostatics and radiation therapy compared to NSCLC.

As a result of the intensive development of methods for treating SCLC, the survival rate of patients receiving modern therapy has increased 4-5 times compared with untreated patients, about 10% of the entire patient population has no signs of the disease within 2 years after the end of treatment, 5-10% live longer 5 years without signs of relapse of the disease, i.e. they can be considered cured, although they are not guaranteed against the possibility of tumor regrowth (or the occurrence of NSCLC).

The diagnosis of SCLC is finally established by morphological examination and is built clinically on the basis of radiological data, which most often reveals the central location of the tumor, often with symptoms of atelectasis and pneumonia and early damage to the lymph nodes of the root and mediastinum. Patients often experience mediastinal syndrome - signs of compression of the superior vena cava, as well as metastatic lesions of the supraclavicular and less commonly other peripheral lymph nodes and symptoms associated with the generalization of the process (metastatic lesions of the liver, adrenal glands, bones, bone marrow, central nervous system).

About two-thirds of patients suffering from SCLC already have signs of metastasis at the first visit, and 10% have brain metastases.

Neuroendocrine paraneoplastic syndromes occur more often than in other forms of lung cancer in SCLC. Research in recent years has made it possible to clarify a number of neuroendocrine characteristics of SCLC and identify markers that can be used to monitor the course of the process, but not for early diagnosis. The markers CYFRA 21-1 and neuron-specific enolase (NSE) are of greatest practical importance when monitoring patients with SCLC. carcinoembryonic antigen (CEA).

The importance of “antioncogenes” (tumor suppressor genes) in the development of SCLC is shown and genetic factors that play a role in its occurrence are identified.

A number of monoclonal antibodies to the surface antigens of small cell lung cancer cells have been isolated, but so far the possibilities of their practical use are limited mainly to the identification of SCLC micrometastases in the bone marrow.

Staging and prognostic factors.

When diagnosing SCLC, 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), CT of the chest and abdominal cavity is performed, as well as CT or MRI of the brain with contrast and bone scanning.

Recently, there have been reports that positron emission tomography (PET) can further clarify the stage of the process.

With the development of new diagnostic techniques, bone marrow puncture has largely lost its diagnostic value, which remains relevant only in the case of clinical signs of bone marrow involvement in the process.

With SCLC, as with other forms of lung cancer, staging is used according to the international TNM system, however, most patients with SCLC at the time of diagnosis already have stages III-IV of the disease, which is why the Veterans Administration Lung Cancer Study Group classification, according to which distinguish between patients with localized SCLC (Limited Disease) and widespread SCLC (Extensive Disease).

In localized SCLC, the tumor lesion is limited to one hemithorax with the involvement of regional and contralateral lymph nodes of the mediastinal root and ipsilateral supraclavicular lymph nodes, when irradiation using a single field is technically possible.

Widespread SCLC is considered to be a process that goes beyond the localized one. Ipsilateral pulmonary metastases and the presence of tumor pleurisy indicates advanced SCLC.

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

Surgical treatment is possible only in the early stages of SCLC - with a primary tumor T1-2 without regional metastases or with damage to bronchopulmonary lymph nodes (N1-2).

However, surgical treatment alone or a combination of surgery and radiation does not provide satisfactory long-term results. A statistically significant increase in life expectancy is achieved using postoperative adjuvant combination chemotherapy (4 courses).

According to the summary data of modern literature, the five-year survival rate of operable patients with SCLC who received combination chemotherapy or combined chemoradiotherapy in the postoperative period is about 39%.

A randomized trial showed the advantage of surgery over radiation therapy as the first stage of complex treatment of technically resectable patients with SCLC; The five-year survival rate for stages I-II in the case of surgery with postoperative chemotherapy was 32.8%.

The feasibility of using neoadjuvant chemotherapy for localized SCLC, when patients underwent surgical treatment after achieving the effect of induction therapy, continues to be studied. Despite the attractiveness of the idea, randomized studies have not yet made it possible to give a clear conclusion about the advantages of this approach.

Even in the early stages of SCLC, chemotherapy is a mandatory component of complex treatment.

In later stages of the disease, the basis of therapeutic tactics is the use of combination chemotherapy, and in the case of localized SCLC, the feasibility of combining chemotherapy with radiation therapy has been proven, and in advanced SCLC, the use of radiation therapy is possible only when indicated.

Patients with localized SCLC have a significantly better prognosis compared to patients with advanced SCLC.

The median survival of patients with localized SCLC using combinations of chemotherapy and radiation therapy in the optimal regimen is 16-24 months with a 40-50% two-year survival rate and a 5-10% five-year survival rate. In a group of patients with localized SCLC who started treatment in good general condition, a five-year survival rate of up to 25% is possible. In patients with advanced SCLC, median survival can be 8–12 months, but long-term disease-free survival is extremely rare.

A favorable prognostic sign for SCLC, in addition to a localized process, is good general condition (Perfomance Status) and, according to some data, female gender.

Other prognostic signs - age, histological subtype of the tumor and its genetic characteristics, serum LDH level - are ambiguously assessed by various authors.

The response to induction therapy also allows one to predict the results of treatment: only achieving a full clinical effect, i.e., complete tumor regression, allows one to count on a long relapse-free period until cure. There is evidence that patients with SCLC who continue to smoke during treatment have worse survival compared to patients who quit smoking.

In case of relapse of the disease, even after successful treatment of SCLC, it is usually not possible to achieve a cure.

Chemotherapy for SCLC.

Chemotherapy is the mainstay of treatment for patients with SCLC.

Classic cytostatics of the 70-80s, such as cyclophosphamide, ifosfamide, nitroso derivatives CCNU and ACNU, methotrexate, doxorubicin, epirubicin, etoposide, vincristine, cisplatin and carboplatin, have antitumor activity in SCLC of the order of 20-50%. However, monochemotherapy is usually not effective enough, the resulting remissions are unstable, and the survival rate of patients receiving chemotherapy with the drugs listed above does not exceed 3-5 months.

Accordingly, monochemotherapy has retained its importance only for a limited group of patients with SCLC whose general condition is not subject to more intensive treatment.

Based on a combination of the most active drugs, combination chemotherapy regimens have been developed, which are widely used in SCLC.

Over the last decade, the combination of EP or EC (etoposide + cisplatin or carboplatin) has become the standard for the treatment of patients with SCLC, replacing the previously popular combinations CAV (cyclophosphamide + doxorubicin + vincristine), ACE (doxorubicin + cyclophosphamide + etoposide), CAM (cyclophosphamide + doxorubicin + methotrexate) and other combinations.

It has been proven that combinations of EP (etoposide + cisplatin) and EC (etoposide + carboplatin) have antitumor activity in advanced SCLC of the order of 61-78% ( full effect in 10-32% of patients). Median survival ranges from 7.3 to 11.1 months.

A randomized trial comparing the combination of cyclophosphamide, doxorubicin and vincristine (CAV), etoposide with cisplatin (EP) and alternating CAV and EP showed equal overall effectiveness of all three regimens (ER -61%, 51%, 60%) with no significant difference in time to progression (4.3, 4 and 5.2 months) and survival (median 8.6, 8.3 and 8.1 months), respectively. Inhibition of myelopoiesis was less pronounced when using EP.

Because cisplatin and carboplatin are equally effective in SCLC and carboplatin is better tolerated, combinations of etoposide with carboplatin (EC) and etoposide with cisplatin (EP) are used as interchangeable therapeutic regimens for SCLC.

The main reason for the popularity of the EP combination is that, having equal antitumor activity with the CAV combination, it inhibits myelopoiesis to a lesser extent compared to other combinations, limiting less the possibilities of using radiation therapy - according to modern concepts, a mandatory component of the treatment of localized SCLC.

Most new modern chemotherapy regimens are based on either adding a new drug to the EP (or EC) combination, or replacing etoposide with a new drug. A similar approach is used for well-known drugs.

Thus, the pronounced antitumor activity of ifosfamide in SCLC served as the basis for the development of the ICE combination (ifosfamide + carboplatin + etoposide). This combination turned out to be highly effective, however, despite the pronounced antitumor effect, severe hematological complications served as obstacles to its widespread use in clinical practice.

At the Russian Scientific Research Center named after. N. N. Blokhin of the Russian Academy of Medical Sciences has developed a combination of AVP (ACNU + etoposide + cisplatin), which has pronounced antitumor activity in SCLC and, most importantly, is effective in brain metastases and visceral metastases.

The AVP combination (ACNU 3-2 mg/m2 on day 1, etoposide 100 mg/m2 on days 4, 5, 6, cisplatin 40 mg/m2 on days 2 and 8, repeated every 6 weeks) was used to treat 68 patients (15 with localized and 53 with advanced SCLC). The effectiveness of the combination was 64.7% with complete tumor regressions in 11.8% of patients and a median survival of 10.6 months. In SCLC metastases to the brain (29 patients evaluated), complete regression as a result of using the AVP combination was achieved in 15 (52% of patients), partial in three (10.3%) with a median time to progression of 5.5 months. Side effects of the AVP combination were of the nature of myelosuppression (leukopenia III-IV stage -54.5%, thrombocytopenia III-IV stage -74%) and were reversible.

New antitumor drugs.

In the nineties of the 20th century, a number of new cytostatics with antitumor activity in SCLC came into practice. These include taxanes (Taxol or paclitaxel, Taxotere or docetaxel), gemcitabine (Gemzar), topoisomerase I inhibitors topotecan (Gicamtin) and irinotecan (Campto), and the vinca alkaloid Navelbine (vinorelbine). A new anthracycline, Amrubicin, is being studied in Japan for SCLC.

Due to the proven possibility of curing patients with localized SCLC using modern chemoradiotherapy, for ethical reasons, clinical trials new antitumor drugs are carried out in patients with advanced SCLC, or in patients with localized SCLC in case of disease relapse.

Table 1
New drugs for advanced SCLC (first line of therapy) / according to Ettinger, 2001.

A drug	Number of units (estimated)	Overall effect (%)	Median survival (months)


Taxotere
Topotecan
Irinotecan
Irinotecan
Vinorelbine
Gemcitabine
Amrubicin

Summary data on the antitumor activity of new antitumor drugs in SCLC are presented by Ettinger in a review in 2001. .

Information is included on the results of the use of new anticancer drugs in previously untreated patients with advanced SCLC (first line chemotherapy). Based on these new drugs, combinations have been developed that are undergoing phase II-III clinical studies.

Taxol (paclitaxel).

In the ECOG study, 36 previously untreated patients with advanced SCLC received Taxol at a dose of 250 mg/m2 as daily intravenous infusions once every 3 weeks. 34% had a partial response, and the calculated median survival was 9.9 months. In 56% of patients, treatment was complicated by stage IV leukopenia, 1 patient died from sepsis.

In the NCTG study, 43 patients with SCLC received similar therapy protected by G-CSF. 37 patients were assessed. The overall effectiveness of chemotherapy was 68%. No overall effects were recorded. Median survival was 6.6 months. Grade IV neutropenia complicated 19% of all chemotherapy courses.

In case of resistance to standard chemotherapy, Taxol at a dose of 175 mg/m2 was effective in 29%, the median time to progression was 3.3 months. .

The pronounced antitumor activity of Taxol in SCLC served as the basis for the development of combination chemotherapy regimens including this drug.

The possibility of combined use in SCLC of combinations of Taxol and doxorubicin, Taxol and platinum derivatives, Taxol with topotecan, gemcitabine and other drugs has been studied and continues to be studied.

The feasibility of using Taxol in combination with platinum derivatives and etoposide is being most actively studied.

In table 2 presents his results. All patients with localized SCLC received additional radiation therapy to the primary lesion and mediastinum simultaneously with the third and fourth cycles of chemotherapy. The effectiveness of the studied combinations was noted with the pronounced toxicity of the combination of Taxol, carboplatin and topotecan.

table 2
Results of three therapeutic regimens including Taxol for SCLC. (Hainsworth, 2001) (30)

Therapeutic regimen	Number of patients II r/l	Overall efficiency	Median survival (months)	Survival	Hematological complications
					Leukopenia III-IV Art.	Thrombocytopenia	Death from sepsis
Taxol 135 mg/m2 Carboplatin AUC-5

Taxol 200 mg/m2 Carboplatin AUC-6 Etoposide 50/100 mg x 10 days. every 3 weeks

Taxol 100 mg/m2 Carboplatin AUC-5 Topotecan 0.75* mg/m2 Zdn. every 3 weeks

p-advanced SCLC
l-localized SCLC

The multicenter randomized study CALGB9732 compared the effectiveness and tolerability of combinations of etoposide 80 mg/m2 on days 1-3 and cisplatin 80 mg/m2 on day 1, repeating the cycle every 3 weeks (group A) and the same combination supplemented with Taxol 175 mg/m 2 - 1 day and G-CSF 5 mcg/kg days 8-18 of each cycle (gr. B).

Based on the experience of treating 587 patients with advanced SCLC who had not previously received chemotherapy, it was shown that the survival of patients in the compared groups did not differ significantly:

In group A, the median survival was 9.84 months. (95% CI 8.69 - 11.2) in group B 10, 33 months. (95% CI 9, 64-11.1); 35.7% (95% CI 29.2-43.7) of patients in group A and 36.2% (95 CI 30-44.3) of patients in group B lived for more than a year. Toxicity, including stage V toxicity. (drug-related death) was higher in group B, which allowed the authors to conclude that the addition of Taxol to combinations of etoposide and cisplatin in the first line of chemotherapy for advanced SCLC increases toxicity without significantly improving treatment outcomes (Table 3).

Table 3
Results of a randomized trial assessing the effectiveness of the additional inclusion of Taxol in the combination of etoposide with cisplatin in 1 line chemotherapy for advanced SCLC (study CALGB9732)

	Number of patients	Survival		Toxicity > III degree.
	Number of patients	Median (months)		neutropenia	thrombocytopenia	neurotoxicity	Lek. death
Etoposide 80 mg/m2 1-3 days, cisplatin 80 mg/m2 - 1 day. every 3 weeks x6		9,84 (8,69- 11,2)	35,7% (29,2-43,7)
Etoposide 80 mg/m2 1-3 days, cisplatin 80 mg/m2 - 1 day, Taxol 175 mg/m2 1 day, G-CSF 5 mcg/kg 4-18 days, every 3 weeks x6		10,33 (9,64-11,1)

From an analysis of summary data from ongoing phase II-III clinical trials, it is clear that the inclusion of Taxol may increase the effectiveness of combination chemotherapy,

increasing, however, the toxicity of some combinations. Accordingly, the feasibility of including Taxol in combination chemotherapy regimens for SCLC continues to be intensively studied.

Taxotere (doietaxel).

Taxotere (docetaxel) entered clinical practice later than Taxol and, accordingly, later began to be studied in SCLC.

During a phase II clinical study in 47 previously untreated patients with advanced SCLC, Taxotere showed an efficacy of 26% with a median survival of 9 months. Neutropenia IV degree complicated treatment in 5% of patients. Febrile neutropenia was registered, one patient died from pneumonia.

The combination of Taxotere and cisplatin was studied as first line chemotherapy in patients with advanced SCLC in the Chemotherapy Department of the Russian Cancer Research Center named after. N. N. Blokhin RAMS.

Taxotere at a dose of 75 mg/m2 and cisplatin 75 mg/m2 were administered intravenously once every 3 weeks. Treatment was continued until progression or intolerable toxicity. In case of complete effect, 2 additional cycles of consolidation therapy were performed.

Of the 22 patients subject to evaluation, a complete effect was recorded in 2 patients (9%) and a partial effect in 11 (50%). Overall effectiveness was 59% (95% CI 48, 3-69.7%).

The median duration of response was 5.5 months, the median survival was 10.25 months. (95% Cl 9.2-10.3). 41% of patients survived 1 year (95% Cl 30.3-51.7%).

The main manifestation of toxicity was neutropenia (18.4% - stage III and 3.4% - stage IV), febrile neutropenia occurred in 3.4%, and there were no drug-related deaths. Non-hematological toxicity was moderate and reversible.

Topoisomerase I inhibitors.

Among the drugs from the group of topomerase I inhibitors for SCLC, topotecan and irinotecan are used.

Topotecan (Gikamtin).

In the ECOG study, topotecan (Hycamtin) at a dose of 2 mg/m2 was administered daily for 5 consecutive days every 3 weeks. In 19 of 48 patients, a partial effect was achieved (efficacy 39%), the median survival of patients was 10.0 months, 39% of patients survived one year. 92% of patients who did not receive CSF had grade III-IV neutropenia and grade III-IV thrombocytopenia. registered in 38% of patients. Three patients died from complications.

As a second-line chemotherapy, topotecan was effective in 24% of patients who had previously responded to treatment and in 5% of refractory patients.

Accordingly, a comparative study of topotecan and the combination of CAV was organized in 211 patients with SCLC who had previously responded to first line chemotherapy (“sensitive” relapse). In this randomized study, topotecan 1.5 mg/m2 was administered intravenously daily for five consecutive days every 3 weeks.

The results of topotecan did not differ significantly from the results of chemotherapy with the CAV combination. The overall efficacy of topotecan was 24.3%, CAV was 18.3%, time to progression was 13.3 and 12.3 weeks, and median survival was 25 and 24.7 weeks, respectively.

Stage IV neutropenia complicated topotecan therapy in 70.2% of patients, CAV therapy in 71% (febrile neutropenia in 28% and 26%, respectively). The advantage of topotecan was a significantly more pronounced symptomatic effect, which is why the US FDA recommended this drug as second-line chemotherapy for SCLC.

Irinotecan (Campto, CPT-II).

Irinotecan (Campto, CPT-II) turned out to have quite pronounced antitumor activity in SCLC.

In a small group of previously untreated patients with advanced SCLC, it was effective at 100 mg/m2 weekly in 47-50%, although the median survival of these patients was only 6.8 months. .

In several studies, irinotecan was used in patients with relapsed disease after standard chemotherapy, and its effectiveness ranged from 16 to 47%.

The combination of irinotecan with cisplatin (cisplatin 60 mg/m2 on day 1, irinotecan 60 mg/m2 on days 1, 8, 15, repeating the cycle every 4 weeks, 4 cycles in total) was compared in a randomized study with the standard combination EP (cisplatin 80 mg/m2 -1 day, etoposide 100 mg/m2 days 1-3) in patients with previously untreated advanced SCLC. The combination with irinotecan (SR) was more effective than the EP combination (overall efficacy 84% versus 68%, median survival 12.8 months versus 9.4 months, 2-year survival 19% versus 5%, respectively).

The toxicity of the compared combinations was comparable: neutropenia was more often complicated by ER (92%) compared to the SR regimen (65%), diarrhea grade III-IV. occurred in 16% of patients receiving CP.

Also noteworthy is the report on the effectiveness of the combination of irinotecan with etoposide in patients with relapsed SCLC (overall effectiveness 71%, time to progression 5 months).

Gemcitabine.

Gemcitabine (Gemzar) at a dose of 1000 mg/m2 escalated to 1250 mg/m2 weekly for 3 weeks, repeating the cycle every 4 weeks, was used in 29 patients with advanced SCLC as 1st line chemotherapy. The overall effectiveness was 27% with a median survival of 10 months. gemcitabine was well tolerated.

The combination of cisplatin and gemcitabine, used in 82 patients with advanced SCLC, was effective in 56% of patients with a median survival of 9 months. .

Good tolerability and results of using gemcitabine in combination with carboplatin in SCLC, comparable to standard regimens, served as the basis for organizing a multicenter randomized trial comparing the results of using the combination of gemcitabine with carboplatin (GC) and the combination of EP (etoposide with cisplatin) in patients with SCLC with a poor prognosis. Patients with advanced SCLC and patients with localized SCLC with unfavorable prognosis factors were included - a total of 241 patients. The GP combination (gemcitabine 1200 mg/m2 on days 1 and 8 + carboplatin AUC 5 on day 1 - every 3 weeks, up to 6 courses) was compared with the EP combination (cisplatin 60 mg/m2 on day 1 + etoposide 100 mg/m2 per os 2 times a day on days 2 and 3 every 3 weeks). Patients with localized SCLC who responded to chemotherapy received additional radiation therapy and prophylactic irradiation of the brain.

The effectiveness of the GC combination was 58%, the EP combination was 63%, median survival was 8.1 and 8.2 months, respectively, with satisfactory tolerability of chemotherapy.

Another randomized trial, including 122 patients with SCLC, compared the results of 2 combinations containing gemcitabine. The PEG combination included cisplatin 70 mg/m2 on days 2, etoposide 50 mg/m2 on days 1-3, gemcitabine 1000 mg/m2 on days 1 and 8. The cycle was repeated every 3 weeks. The PG combination included cisplatin 70 mg/m2 on day 2, gemcitabine 1200 mg/m2 on days 1 and 8 every 3 weeks. The PEG combination was effective in 69% of patients (complete effect in 24%, partial in 45%), the PG combination in 70% (complete effect in 4% and partial in 66%).

The study of the possibility of improving the results of treatment of SCLC through the use of new cytostatics continues.

It is still difficult to clearly determine which of them will change modern capabilities treatment of this tumor, but the fact that the antitumor activity of taxanes, topoisomerase I inhibitors and gemcitabine has been proven allows us to hope for further improvement of modern therapeutic regimens for SCLC.

Molecularly targeted "targeted" therapy for SCLC.

A fundamentally new group of antitumor drugs are molecularly targeted, so-called targeted drugs that have true selectivity of action. The results of molecular biology studies provide convincing evidence that the 2 main subtypes of lung cancer (SCLC and NSCLC) have both common and significantly different genetic characteristics. Due to the fact that SCLC cells, unlike NSCLC cells, do not express epidermal growth factor receptors (EGFR) and cycloxygenase 2 (COX2), there is no reason to expect the possible effectiveness of drugs such as Iressa (ZD1839), Tarceva (OS1774) or Celecoxib, which are being intensively studied in NSCLC.

At the same time, up to 70% of SCLC cells express the Kit proto-oncogene, which encodes the CD117 tyrosine kinase receptor.

The Kit tyrosine kinase inhibitor Gleevec (ST1571) is in clinical trials for SCLC.

First results of using Gleevec at a dose of 600 mg/m2 orally daily as the only medicinal product in previously untreated patients with advanced SCLC showed its good tolerability and the need to select patients depending on the presence of a molecular target (CD117) in the patient’s tumor cells.

Among the drugs in this series, Tirapazamine, a hypoxic cytotoxin, and Exizulind, which affects apoptosis, are also being studied. The feasibility of using these drugs in combination with standard therapeutic regimens in hopes of improving patient survival is being assessed.

Therapeutic tactics for SCLC

Therapeutic tactics for SCLC are determined primarily by the prevalence of the process and, accordingly, we specifically focus on the issue of treating patients with localized, advanced and recurrent SCLC.

Some problems are discussed in advance general: intensification of doses of antitumor drugs, the advisability of maintenance therapy, treatment of elderly patients and patients in severe general condition.

Dose intensification for chemotherapy of SCLC.

The question of the feasibility of intensifying doses of chemotherapy in SCLC has been actively studied. In the 80s, there was an idea that the effect was directly dependent on the intensity of chemotherapy. However, a number of randomized studies have not revealed a clear correlation between the survival of patients with SCLC and the intensity of chemotherapy, which was confirmed by a meta-analysis of materials from 60 studies devoted to this problem.

Arrigada et al. used a moderate initial intensification of the therapeutic regimen, comparing cyclophosphamide in a randomized trial course dose 1200 mg/m2 + cisplatin 100 mg/m2 and cyclophosphamide 900 mg/m2 + cisplatin 80 mg/m2 as 1 treatment cycle (further therapeutic regimens were the same). Among 55 patients who received higher doses of cytotoxic drugs, the two-year survival rate was 43%, compared with 26% for 50 patients who received lower doses. Apparently, the favorable moment was precisely the moderate intensification of induction therapy, which made it possible to obtain a pronounced effect without a significant increase in toxicity.

An attempt to increase the effectiveness of chemotherapy by intensifying therapeutic regimens using autologous bone marrow transplantation, peripheral blood stem cells and the use of colony-stimulating factors (GM-CSF and G-CSF) showed that despite the fact that such approaches are fundamentally possible and the percentage of remissions can be increased, The survival rate of patients cannot be significantly increased.

In the chemotherapy department of the Clinical Research Center of the Russian Academy of Medical Sciences, 19 patients with a localized form of SCLC received therapy according to the CAM regimen in the form of 3 cycles with an interval of 14 days instead of 21 days. GM-CSF (Leukomax) at a dose of 5 μg/kg was administered subcutaneously daily for days 2–11 of each cycle. When compared with the historical control group (25 patients with localized SCLC who received CAM without GM-CSF), it turned out that despite the intensification of the regimen by 33% (the dose of cyclophosphamide was increased from 500 mg/m2/week to 750 mg/m2/week , Adriamycin from 20 mg/m2/week to 30 mg/m2/week and Methotrexate from 10 mg/m2/week to 15 mg/m2/week), the treatment results in both groups are identical.

A randomized study showed that the use of GCSF (lenograstim) at a dose of 5 mcg/kg per day in the intervals between VICE cycles (vincristine + ifosfamide + carboplatin + etoposide) allows increasing the intensity of chemotherapy and increasing two-year survival, but the toxicity of the intensified regimen significantly increases (out of 34 patients, 6 died from toxicosis).

Thus, despite ongoing research into early intensification of therapeutic regimens, there is no convincing evidence of the benefits of this approach. The same applies to the so-called late intensification of therapy, when patients who have achieved remission after conventional induction chemotherapy are administered high doses of cytostatics under the protection of autologous bone marrow or stem cell transplantation.

In a study by Elias et al, patients with localized SCLC who achieved complete or significant partial remission after standard chemotherapy underwent high-dose consolidation chemotherapy with autologous bone marrow transplantation and radiation. After such intensive therapy, 15 of 19 patients had complete tumor regression, and the two-year survival rate reached 53%. The late intensification method is the subject of clinical research and has not yet gone beyond the scope of a clinical experiment.

Maintenance therapy.

The idea that long-term maintenance chemotherapy can improve long-term outcomes in patients with SCLC has been refuted by a number of randomized trials. There was no significant difference in survival between patients who received long-term maintenance therapy and those who did not. Some studies have shown an increase in time to progression, which, however, was achieved at the expense of a decrease in the quality of life of patients.

Modern therapy for SCLC does not provide for the use of maintenance therapy, either with cytostatics or with the help of cytokines and immunomodulators.

Treatment of elderly patients with SCLC.

The possibility of treating elderly patients with SCLC is often questioned. However, age even over 75 years cannot serve as a basis for refusing treatment for patients with SCLC. In cases of severe general condition and the inability to use chemoradiotherapy, treatment of such patients can begin with the use of oral etoposide or cyclophosphamide, followed, if the condition improves, by switching to standard chemotherapy EC (etoposide + carboplatin) or CAV (cyclophosphamide + doxorubicin + vincristine).

Modern treatment options for patients with localized SCLC.

Efficiency modern therapy for localized SCLC ranges from 65 to 90%, with complete tumor regression in 45-75% of patients and a median survival of 18-24 months. Patients who start treatment in good general condition (PS 0-1) and respond to induction therapy have a chance of five years of disease-free survival.

The combined use of combination chemotherapy and radiation therapy for localized forms of small cell lung cancer has gained universal acceptance, and the benefits of this approach have been proven in a number of randomized studies.

A meta-analysis of data from 13 randomized trials evaluating the role of chest irradiation in combination with combination chemotherapy for localized SCLC (2140 patients) showed that the risk of death in patients receiving chemotherapy in combination with radiation was 0.86 (95% confidence interval 0.78 - 0.94) in relation to patients who received only chemotherapy, which corresponds to a 14% reduction in the risk of death. Three-year overall survival with the use of radiation therapy was better by 5.4 + 1.4%, which confirmed the conclusion that the inclusion of radiation significantly improves the results of treatment of patients with localized SCLC.

N. Murray et al. studied the issue of the optimal timing of radiation therapy in patients with localized SCLC receiving alternating courses of combination chemotherapy with CAV and EP. 308 patients were randomized to receive 40 Gy in 15 fractions starting in the third week, simultaneously with the first EP cycle, and to receive the same radiation dose during the last EP cycle, i.e., from week 15 of treatment. It turned out that although the percentage of complete remissions did not differ significantly, relapse-free survival was significantly higher in the group who received radiation therapy earlier.

The optimal sequence of chemotherapy and radiation, as well as specific therapeutic regimens, are the subject of further research. In particular, a number of leading American and Japanese specialists prefer the use of a combination of cisplatin with etoposide, starting radiation simultaneously with the first or second cycle of chemotherapy, while in the Research Center of the Russian Academy of Medical Sciences, radiation therapy in a total dose of 45-55 Gy is more often carried out sequentially.

A study of long-term liver outcomes in 595 patients with inoperable SCLC who completed therapy at the Cancer Research Center more than 10 years ago showed that the combination of combination chemotherapy with irradiation of the primary tumor, mediastinum and supraclavicular lymph nodes made it possible to increase the number of clinical complete remissions in patients with a localized process to 64%. The median survival of these patients reached 16.8 months (in patients with complete tumor regression, the median survival is 21 months). 9% have been alive without signs of the disease for more than 5 years, that is, they can be considered cured.

The optimal duration of chemotherapy for localized SCLC is not entirely clear, but there is no evidence of improved survival in patients treated for more than 6 months.

The following combination chemotherapy regimens have been tested and become widespread:
EP - etoposide + cisplatin
EC - etoposide + carboplatin
CAV - cyclophosphamide + doxorubicin + vincristine

As mentioned above, the effectiveness of the EP and CAV regimens for SCLC is almost the same, however, the combination of etoposide with cisplatin, which inhibits hematopoiesis less, is easier to combine with radiation therapy.

There is no evidence of benefit from alternating courses of CP and CAV.

The feasibility of including taxanes, gemcitabine, topoisomerase I inhibitors and targeted drugs in combination chemotherapy regimens continues to be studied.

Patients with localized SCLC who achieve complete clinical remission have a 60% actuarial risk of developing brain metastases within 2-3 years of starting treatment. The risk of developing brain metastases can be reduced by more than 50% when using prophylactic brain irradiation (POI) with a total dose of 24 Gy. A meta-analysis of 7 randomized trials evaluating POM in patients in complete remission showed a reduction in the risk of brain damage, improvement in disease-free survival and overall survival in patients with SCLC. The three-year survival rate increased from 15 to 21% with the use of prophylactic cerebral irradiation.

Principles of therapy for patients with advanced SCLC.

In patients with advanced SCLC, in whom the main treatment method is combination chemotherapy, and radiation is carried out only according to special indications, the overall effectiveness of chemotherapy is 70%, but complete regression is achieved only in 20% of patients. At the same time, the survival rate of patients who achieve complete tumor regression is significantly higher than that of patients treated with a partial effect, and approaches the survival rate of patients with localized SCLC.

For SCLC metastases to the bone marrow, metastatic pleurisy, and metastases to distant lymph nodes, combination chemotherapy is the treatment of choice. For metastatic lesions of the mediastinal lymph nodes with compression syndrome of the superior vena cava, it is advisable to use combined treatment (chemotherapy in combination with radiation therapy). For metastatic lesions of the bones, brain, and adrenal glands, radiation therapy is the method of choice. For brain metastases, radiation therapy at 30 Gy gives a clinical effect in 70% of patients, and in half of them complete regression of the tumor is recorded according to CT data. Recently, data have emerged on the possibility of using systemic chemotherapy for SCLC metastases to the brain.

Experience of the Russian Cancer Research Center named after. N. N. Blokhin Russian Academy of Medical Sciences for the treatment of 86 patients with central nervous system lesions showed that the use of combination chemotherapy can lead to complete regression of SCLC metastases to the brain in 28.2% and partial regression in 23%, and in combination with brain irradiation the effect is achieved in 77.8% of patients with complete tumor regression in 48.2%. The problems of complex treatment of SCLC metastases in the brain are discussed in the article by Z. P. Mikhina and co-authors in this book.

Therapeutic tactics for recurrent SCLC.

Despite high sensitivity to chemotherapy and radiation therapy, SCLC mostly recurs, and in such cases the choice of therapeutic tactics (2nd line chemotherapy) depends on the response to the first line of therapy, the time interval that has passed since its completion and on the nature of tumor spread (localization of metastases).

It is customary to distinguish between patients with sensitive relapse of SCLC who had a complete or partial effect from first-line chemotherapy and progression of the tumor process no earlier than 3 months after the end of induction therapy, and patients with refractory relapse who progressed during induction therapy or less than 3 months after its end. .

The prognosis for patients with relapsed SCLC is extremely unfavorable and there is no reason to expect a cure. It is especially unfavorable for patients with refractory relapse of SCLC, when the median survival after detection of relapse does not exceed 3-4 months.

In case of sensitive relapse, an attempt may be made to re-use the therapeutic regimen that was effective during induction therapy.

For patients with refractory relapse, it is advisable to use antitumor drugs or their combinations that were not used during induction therapy.

The response to chemotherapy for relapsed SCLC depends on whether it is a sensitive or refractory relapse.

Topotecan was effective in 24% of patients with sensitive relapse and 5% of patients with resistant relapse.

The effectiveness of irinotecan in sensitive relapsed SCLC was 35.3% (time to progression 3.4 months, median survival 5.9 months); in refractory relapse, the effectiveness of irinotecan was 3.7% (time to progression 1.3 months. , median survival 2.8 months).

Taxol at a dose of 175 mg/m2 for refractory relapsed SCLC was effective in 29% of patients with a median time to progression of 2 months. and median survival of 3.3 months. .

A study of Taxotere in relapsed SCLC (without dividing into sensitive and refractory) showed its antitumor activity of 25-30%.

Gemcitabine in refractory relapsed SCLC was effective in 13% (median survival 4.25 months).

General principles modern tactics treatment of patients with SCLC can be formulated as follows:

For resectable tumors (T1-2 N1 Mo), surgery followed by postoperative combination chemotherapy (4 courses) is possible.

The feasibility of using induction chemotherapy and chemoradiotherapy followed by surgery continues to be studied, but convincing evidence of the benefits of this approach has not yet been obtained.

At inoperable tumors(localized form) combination chemotherapy (4-6 cycles) in combination with irradiation of the tumor area of the lung and mediastinum is indicated. Maintenance chemotherapy is not appropriate. If complete clinical remission is achieved, preventive irradiation of the brain is performed.

In the presence of distant metastases (a common form of SCLC), combination chemotherapy is used, radiation therapy is carried out according to special indications (metastases to the brain, bones, adrenal glands).

Currently, the possibility of curing about 30% of patients with SCLC in the early stages of the disease and 5-10% of patients with inoperable tumors has been convincingly proven.

The fact that in recent years a whole group of new antitumor drugs active in SCLC has appeared allows us to hope for further improvement of therapeutic regimens and, accordingly, improved treatment outcomes.

A list of references for this article is provided.
Please, introduce yourself.