At the end of the last century, all lung cancer was divided according to the effectiveness of chemotherapy (CT) into two options: poorly responsive non-small cell lung cancer (NSCLC) and sensitive small cell cancer (SCLC). In all forms, one and a half dozen chemotherapy drugs are active, but in the small cell variant, the activity of some cytostatics is twice as high.
Chemotherapy for non-small cell lung cancer
Eight out of ten malignant cancers are non-small cell cancers. lung tumors, predominantly adenocarcinoma and squamous cell. The leading method of treatment is surgery, and drug treatment is used in conjunction with radiation for inoperable tumors before or, rarely, after surgery. The operation is possible only in every tenth person, but after it in eight out of ten patients different time The question of chemotherapy is raised.
Drug treatment is required for patients with an advanced tumor in the lung and for distant metastases after primary treatment. To improve the conditions of surgical intervention, preoperative chemotherapy is used, postoperative chemotherapy can reduce the likelihood of relapse.
What therapy is used for lung cancer
More than ten drugs can be used for NSCLC; many drug regimens are most effective, but only combination with platinum derivatives increases life expectancy. Platinum drugs have equal effectiveness, but different toxicity: cisplatin “hits the kidneys”, and carboplatin “spoils the blood”. Cytostatics of other groups are used when platinum is contraindicated.
In primary chemotherapy, two drugs give better results than one. A three-drug regimen can lead to more pronounced regression of the tumor node, but is more difficult to tolerate.
In the case of squamous cell variant, the platinum derivative together with gemzar has an advantage; in case of adenocarcinoma, also in combination with Alimta.
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Optimal chemotherapy for progression of lung cancer
With continued increase malignant tumor against the background of primary drug treatment, it is necessary to change antitumor drugs to “second line” chemotherapy. In this situation, it is sufficient to use only one drug, in clinical studies a multidrug combination showed no benefit.
When malignant growth continues after a change in therapy, they resort to the “third line” of chemotherapy; today the targeted agent erlotinib is recommended, but other cytostatics are not prohibited.
When the third approach is not successful, further selection of an effective combination of drugs is possible, but achieving the result is accompanied by significant toxic manifestations, and the result itself is short-lived, so the recommendations suggest best supportive care - the best symptomatic therapy.
How many courses do you need to take?
If non-small cell lung cancer continues to progress during treatment, then conducting more than 4 short courses does not make sense.
At good effect after the “first line”, maintenance chemotherapy can be performed, usually with a non-platinum drug or erlotinib for EGFR mutations. It is not mandatory, but should be offered to the patient if tolerated. Maintenance treatment is stopped when signs of continued tumor growth are detected.
When is chemotherapy needed before surgery?
Non-small cell cancer cannot be cured without surgery, but in three quarters of patients the disease is diagnosed at a significant size lung tumors, accordingly, the results of surgical treatment do not promise a long life.
Preoperative chemotherapy helps change the percentage of five-year survival, reduce the likelihood of metastasis, especially when using platinum derivatives, which reduce tumor conglomerate in the lung and lymph nodes. The result is achieved in half of the treated patients, and in eight out of ten it is possible to achieve radical surgery. In addition, preoperative chemotherapy is tolerated with less toxicity, and 3 courses are administered every 21 days.
When the process spreads to the lymph nodes of the mediastinum, the combination of chemotherapy with radiation gives a better result than surgery. But in case of an initially inoperable process, irradiation is preferable at the first stage if there are no contraindications to it, and after that they resort to drug therapy.
Valery Zolotov
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Chemotherapy is a treatment used to remove cancer cells using drugs and various means against prevention . This procedure It is used in different ways: sometimes it can be done independently, and sometimes it is done together with treatment with rays.
If a sick person has developed early-stage small cell cancer, then this course of treatment is considered very effective and useful.
Non-small cell cancer is more difficult to treat with this method because it is more resistant. Chemotherapy is generally used for most patients. And only a few have non-small cell cancer different stages who are undergoing a special course of treatment.
Chemotherapy treatment for lung cancer
Medicines are used not only at the beginning of the course of treatment, but also after, namely in the rehabilitation process. Medications are selected for each patient, taking into account individual characteristics. For small cell lung cancer, the course of treatment is carried out after the tumor has been detected and the stage of development of the disease has been taken into account.
Lung cancer is divided into the following types:
- Localized – with this type of disease there is a large percentage full recovery person. To do this, you need to undergo a wide course of chemotherapy. Medicines are administered intravenously;
- When using chemotherapy as a treatment, some nuances must be taken into account: the gender and age of the patient. This data is necessary in order to correctly prescribe the course of treatment and the right amount of medication, as well as to achieve high efficiency. In addition, you need to know the size of the tumor in the lungs, for this you need to special diagnostics, which helps detect cancer cells in the body. And of course, you need to know at what stage the tumor is now. Chemotherapy has many side effects, so it is best to be constantly examined by a doctor so that this disease can be detected in the early stages of development.
Medicines for treating cancer of different stages with chemotherapy
Nowadays, pharmaceuticals are very developed. Medicines are constantly being produced that can fight many diseases. A huge number of drugs have been produced for the treatment of lung cancer, which are usually prescribed after surgery:
- "Cyclophosphamide";
- "5-fluorouracil";
- "Metatrexate".
These drugs have side effects after long-term use.
The following drugs are used for chemotherapy treatment:
Today, many scientists are working to improve and develop new and more effective drugs that can cure cancer.
Efficacy after chemotherapy for lung cancer.
Often during and after chemotherapy treatment, the patient has a complete loss of appetite.
In this case, to nutrition must be treated with extreme caution and attention. According to many recommendations, you need to eat only in small portions, about seven times a day; more is not advisable. This is not forever, but only for a while until the patient completes the course of chemotherapy.
Preparing the patient for chemotherapy
How to eat properly is outlined above. A lot depends on food, namely the overall health of a person. In addition, food is the most important source of energy and strength. Also, if you wish, you can consult with nutritionists about the correct nutrition , they can create the right menu based on your favorite dishes.
It should be borne in mind that with such a disease you only need to lead a healthy lifestyle: in no case should you drink alcohol or smoke. Calmness in life will also not be superfluous; you should not be too nervous.
How long do they live with lung cancer?
Basically, a large number of patients die not from the disease itself, but from huge amount chemical substances that enter the body along with medications. A person who, on the recommendation of a doctor, undergoes a whole course of treatment can die not only from cancer, but also from any other disease, because the body is very weakened and is not able to fight various kinds of viruses.
No one can say for sure how long people live after such treatment, because everything is individual. But doctors say what needs to be done to make life last much longer. By following doctors' recommendations, you can extend your life.
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Causes and symptoms of lung cancer (Read in 6 minutes) |
Chemotherapy treatment for ovarian cancer and nutrition after it (Read in 4 minutes) |
At the moment, chemotherapy for lung cancer is the treatment method that brings the greatest results. It involves the use of cytotoxic (anti-cancer) drugs to destroy and disrupt the growth of diseased cancer cells.
Chemotherapy is prescribed by an oncologist and is carried out in cycles of usually three to four weeks.
When and how chemotherapy treatment is prescribed
Chemotherapy for lung cancer is prescribed taking into account the stage and extent of the disease, as self-treatment, as well as in combination with radiotherapy (radiation therapy).
“Chemotherapy” is the main remedy for getting rid of small cell lung cancer, since it responds very well to chemotherapy. Also, a feature of small cell cancer is that it often spreads beyond the diseased lung. And the drugs used in chemotherapy circulate in the blood throughout the body. And so they can treat cells that have broken off from the lung tumor and spread to other organs.
In the case of small cell lung cancer, chemotherapy is used alone or in combination with radiotherapy. When the cancer is operable, the procedure may be done before surgery to reduce the size of the cancer. After surgery (sometimes along with x-ray therapy), the doctor will prescribe chemotherapy to try to kill any diseased cells that may remain in the body.
Chemotherapy is also used to treat non-small cell lung cancer. It may be prescribed before or after surgery. It will help shrink the cancer and make the tumor easier to remove.
In the early stages of non-small cell cancer, chemotherapy will help reduce the risk of recurrence after surgery. For this type of disease, “chemistry” can be used in combination with radiotherapy. Especially when surgery is not recommended for the patient for a number of reasons.
For advanced cancer, chemotherapy is more supportive. It can help a patient live longer if the disease can no longer be cured.
Chemotherapy is often prohibited for patients in poor health. But receiving “chemistry” is not prohibited for older people.
Chemotherapy drugs and procedure
The following drugs are most commonly used for chemotherapy:
- "Cisplatin";
- "Taxol" (Paclitaxel);
- "Docetaxel";
- "Navelbine" (Vinorelbine);
- "Gemzar" (Gemcitabine);
- "Kamptosar";
- Pemetrexed.
Often a combination of 2 drugs is used for treatment. Experience shows that adding a third chemotherapy drug does not provide significant benefit and often causes many side effects. And single-drug chemotherapy is sometimes used for people who cannot tolerate combination chemotherapy due to poor overall health or old age.
For reference: doctors usually carry out chemotherapy for 1-3 days. This is followed by a short rest to give the body time to recover. Chemo cycles typically last 3 to 4 weeks.
For advanced disease, chemotherapy is often given over four to six cycles. The findings suggest that such long-term treatment, called maintenance therapy, curbs cancer progression and can help people live longer.
Possible side effects and negative effects
Chemotherapy drugs affect cells that multiply quickly. In this regard, they are used against cancer cells. But the remaining (healthy) cells in the body, such as cells spinal cord, intestinal and oral mucosa, as well as hair follicles, also have the ability to rapid division. Unfortunately, drugs can also penetrate into these cells, which leads to certain undesirable consequences.
The negative effects of chemotherapy depend on the dose and type of medication, as well as the length of time you take it.
The main side effects are:
- the appearance of ulcers in the mouth and tongue;
- significant reduction hairline and baldness;
- lack of appetite;
- vomiting and nausea;
- disorders gastrointestinal tract– diarrhea, constipation;
- increased likelihood of infections (due to the decrease in the number of leukocytes in the blood);
- bleeding (due to a decrease in the number of red blood cells);
- general fatigue and tiredness.
These side effects almost always stop when treatment is completed. And modern medicine has many ways to reduce the negative effects of chemotherapy. For example, there are drugs that help prevent vomiting and nausea and reduce hair loss.
The use of certain drugs, such as Cisplatin, Docetaxel, Paclitaxel, can cause peripheral neuropathy - nerve damage. Sometimes this can lead to symptoms (mainly in the extremities) such as burning, pain, tingling, sensitivity to heat or cold, and weakness. For most people, these symptoms go away once treatment is stopped.
Patients should always inform their doctor about any side effects they notice. In some cases, the dose of chemotherapy drugs may be reduced. And sometimes it is necessary to stop treatment for a while.
Nutrition during chemotherapy
People undergoing chemotherapy must eat well and properly. This will help them feel better and stay strong, prevent loss bone tissue and muscle mass. Good food helps fight infections and has great value in treating cancer and improving quality of life. Food should be enriched with vitamins and beneficial microelements.
Since the body is under stress during chemotherapy, it is necessary to consume plenty of protein to promote healing and get the immune system functioning again. Red meat, chicken, and fish are excellent sources of protein and iron. There is a lot of protein in foods such as cheese, beans, nuts, eggs, milk, cottage cheese, yogurt.
Because of mouth ulcers that appear during chemotherapy, it may be difficult for a patient to drink citrus juices or eat citrus fruits, which are among the most common sources of vitamin C. They can be replaced with alternative ways to obtain this vitamin - peaches, pears, apples, as well as juices and nectars from these fruits.
Important! All fruits and vegetables need to be washed very well because the immune system becomes more susceptible to contaminants in food.
Chemotherapy and radiation can also lead to dehydration. And some medications can cause kidney failure if they are not eliminated from the body. Therefore, it is essential to stay hydrated during cancer treatment.
Chemotherapy currently shows good results in the treatment of lung cancer. However, many chemotherapy drugs cause side effects. Therefore, it is necessary to constantly keep in touch with your attending physician, who will help you choose proper care to improve the patient's quality of life.
Today the most common oncological pathology Lung cancer is considered to have a high mortality rate. Previously, this disease was the prerogative of people in the older age group, but now cancer is “younger.” Modern diagnostic methods make it possible to identify the disease at an early stage, which greatly facilitates the treatment process. For lung cancer, a comprehensive approach is used, which includes chemotherapy, radiation therapy and surgery. Chemotherapy for lung cancer is highly effective and significantly increases the chances of recovery.
What is lung cancer
Every year, up to a million cases of lung cancer are diagnosed worldwide. Statistics regarding the positive prognosis are disappointing - 6 fatal episodes per 10 cases. On the territory of the Russian Federation, this figure is 12% of the total incidence, while mortality is 15% of all identified cases.
Lung cancer is prevalent mainly among the male population. Oncologists explain this distribution by the reasons that led to the pathological process - smoking.
The classification is based on the localization of the pathological focus:
- central - located in the lumen of the large bronchi in the roots of the lung. As it develops, it leads to complete occlusion, as a result the lung cannot function normally;
- peripheral - an extremely dangerous option, since it occupies the area along the edge of the lung fields, remains “silent” for a very long time, and makes itself felt only with a significant increase in size;
- massive – combined damage by both options.
Stages of cancer development
There are 4 main stages of development of lung cancer, with the third being divided into 2 subtypes:
- Zero. At an early stage, pathological cells are formed, which cannot be detected by instrumental methods. Clinical manifestations are not detected at stage zero.
- First. The most favorable for prescribing therapy, since treatment during this period can bring the maximum positive effect. The size of the lesion does not exceed three centimeters in maximum length. There is no reaction of regional lymph nodes. Cancer is detected at the first stage in only 10%, which determines the importance of annual fluorographic examinations.
- Second. The size of the tumor node varies from 3 to 5 centimeters, which allows them to be visualized on x-ray. Accompanied by specific complaints - cough, hemoptysis, syndromes of the cardiovascular system, weight loss, increased fatigue.
- Stage 3a. The size of the tumor increases, which leads to increased symptoms. Involvement of the mediastinal lymph nodes is noted. The favorable prognosis is about 30%.
- Stage 3b. Metastases appear both in the lung itself and in the thoracic vertebrae, ribs, and sternum. May be accompanied by pathological fractures.
- Fourth. Multiple foci of dropouts that spread hematogenously. The chances of recovery are minimal, so chemotherapy may often not be prescribed at stage 4 of lung cancer. In such a situation, they resort to symptomatic treatment(palliative).
Based on this division, oncologists select the type of therapy.
Treatment options for lung cancer
Based on the results of all research, a set of therapeutic measures is created. The main methods for lung cancer are surgery, chemotherapy and radiation therapy. It is an integrated approach using all techniques that can give a positive effect.
Surgical treatment of lung cancer
The goal of the operation is to remove as much of the tumor node as possible in order to reduce compression on adjacent tissues. To achieve a significant effect, it is always combined with chemotherapy and radiation therapy.
There are several approaches surgical intervention(laparoscopically, transthoracically), which depend on the type, size and location of the tumor.
Chemotherapy
Is the main method of treatment cancer diseases. The mechanism of action of the drugs is based on a massive effect on the cellular apparatus of the tumor with its destruction. Depending on the combination with the surgical approach, chemotherapy for lung cancer is of three types:
- Neoadjuvant, which is prescribed before surgery. Designed to destroy tumor cells and stop metastasis.
- Adjuvant, used after surgery or radiation therapy for the final elimination of the remaining elements of cancer.
- Targeted is a high-precision technique based on a targeted effect on the node with inhibition of growth and division. There is also a restriction in the blood supply to the cancer. The technique can be used both as independent therapy and in combination with other options.
Indications and contraindications for chemotherapy
The conditions for choosing this approach are:
- localization of the node and the degree of impact on surrounding tissues;
- the types of cells that formed the tumor;
- the presence of intraorgan and distant metastases;
- lymph node reaction.
Leukemia, rhabdomyosarcoma, hemoblastosis, chorionic carcinoma make it possible to conduct a course of chemotherapy for lung cancer.
Before starting treatment, the doctor assesses the risks and expected side effects. A well-designed course of chemotherapy increases the likelihood of successful treatment.
Contraindications for chemotherapy:
- thrombocytopenia;
- infectious diseases in the acute period;
- pregnancy, especially in the first trimester;
- renal, liver, heart failure;
- severe exhaustion.
The peculiarity of these contraindications is the possibility of correction. Therefore, the treating doctor will initially remove the restrictions and then begin specific chemotherapy treatment.
Options for drugs prescribed during chemotherapy
There are more than 60 options for drugs used during chemotherapy. The most common are Cisplatin, Carboplatin, Gemcitabine, Vinorelbine, Paclitaxel and Docetaxel. Most often they create combinations of them.
The development of oncology science does not stand still; new cytostatic drugs are being created. It is possible that during treatment you may be offered to participate in clinical trials. Of course, you have the right to refuse.
Conditions for chemotherapy
Chemistry (cytostatics) for lung cancer is most often administered intravenously in a hospital setting. The doctor selects the regimen and dose based on the histological appearance of the tumor, the stage of the disease and the individual characteristics of the patient.
Upon completion of the course of chemotherapy, the patient is given a recovery break for 2 weeks. This will be followed by the next course, their number is determined by the therapy protocol and effectiveness. Repeated testing is due to the adaptive characteristics of cancer cells to the toxic effects of drugs. To smooth out side effects, symptomatic therapy is prescribed.
A tablet version of taking chemotherapy is also possible. The advantage is that you can drink them on an outpatient basis.
Side effects
The effectiveness of this method is very high, especially with early detection. A feature of the standard regimen of drugs is their non-selective effect on the cells of the body. Therefore, the consequences of chemotherapy for lung cancer affect all systems:
- hematopoiesis (blood formation);
- dysfunction of the gastrointestinal tract in the form of dyspeptic manifestations;
- the massive effect of drugs on all rapidly dividing cells (not only cancer cells) is accompanied by hair loss (alopecia);
- psycho-emotional disorders (depression);
- It is possible that secondary infections may occur due to a decrease in the body’s protective functions.
It is important to understand that these manifestations are inevitable, they must be accepted as a given. On the other hand, they are temporary. Quite often, after completing the courses, all physiological processes return to normal. You need to survive this period in your life and under no circumstances stop treatment.
Palliative medicine
A new direction in patient management is palliative chemotherapy for lung cancer. This approach is used for a group of patients who are all possible methods have been provided, but the process is constantly progressing. Designed to improve the quality of life of inoperable patients by leveling pain syndromes, correction of the psycho-emotional background.
Radiotherapy
Based on the effect of a beam of gamma rays on the tumor process. In this case, the death of cancer cells is noted due to the cessation of growth and division. The rays affect not only the tumor itself, but also nearby metastases, which gives a complex effect. The use of radiotherapy is also possible for small cell lung cancer. Recent medical advances in radiation therapy include:
- remote technique, when the effect is carried out using an external (outside the body) source of x-rays;
- high-dose technology, which is based on the introduction of a special source generating rays into the patient’s body.
The latest advancement is the RAPID Arc therapy. Feature - targeted impact exclusively on the cancer node, while healthy tissue is not damaged. It is accompanied by visual control of the manipulation with the ability to adjust the flow intensity and direction angle. Application is limited by the prevalence of the process.
If the cancer extends beyond the lungs, then this technique is not performed.
conclusions
Lung cancer is a terrible diagnosis with a high mortality rate. It is impossible to cure this disease on your own. Waiting tactics are fraught with tumor enlargement to the extent that methods modern medicine they won't be able to help.
Chemotherapy is a recognized and effective method of suppression further development oncology. Of course, it has a number of side effects, but the effectiveness successfully covers them.
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PRACTICAL ONCOLOGY. T.6, No. 4 - 2005
GU RONC im. N.N.Blokhin RAMS, Moscow
M.B. Bychkov, E.N. Dgebuadze, S.A. Bolshakova
Research into new therapies for SCLC is currently underway. On the one hand, new regimens and combinations with lower levels of toxicity and greater efficiency 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-smoking patients.
SCLC is one of the most malignant tumors and is characterized by a short history, rapid course, and has a tendency to metastasize early. Small cell lung cancer is a tumor that is highly sensitive to chemotherapy, and an objective response can be obtained in most patients. When complete tumor regression is achieved, prophylactic irradiation of the brain is performed, which reduces the risk of distant metastasis and increases overall survival.
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), computed tomography (CT) of the chest and abdominal cavity is performed, as well as CT or magnetic resonance imaging (MRI) of the brain (with contrast) and bone scanning.
IN Lately There have been reports that positron emission tomography can further clarify the stage of the process.
For SCLC, as for other forms of lung cancer, staging is used international system TNM, however, the majority of patients with SCLC already have stages III-IV of the disease at the time of diagnosis; therefore, the classification according to which localized and widespread forms of the disease are distinguished has not lost its significance to this day.
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. lymph nodes, when it is technically possible to perform irradiation using a single field.
A common stage of the disease is considered to be a process when the tumor lesion is not limited to one hemithorax, with the presence of contralateral lymphatic metastases or tumor pleurisy.
The stage of the process, which determines therapeutic options, is the main prognostic factor in SCLC.
Prognostic factors:
1. Extent of the process: patients with a localized process (not extending beyond the chest) achieve better results with chemoradiotherapy.
2. Achieving complete regression of the primary tumor and metastases: there is a significant increase in life expectancy and there is the possibility of complete recovery.
3. General condition of the patient: patients who begin treatment in good condition have a higher treatment efficiency, longer survival than patients in serious condition, exhausted, with severe symptoms diseases, hematological and biochemical changes.
Surgical treatment is indicated only for early stages of SCLC ( T 1-2 N 0—1). It should be supplemented with postoperative chemotherapy (4 courses). In this group of patients 5 -year survival rate is 39 % [ 33 ].
Radiation therapy leads to tumor regression in 60-80% of patients, but alone it does not increase life expectancy due to the appearance of distant metastases [ 9 ].
Chemotherapy is the cornerstone 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%. In table 1 shows the schemes of modern combination 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 of 1824 months. Patients who start treatment in good general condition (PS 0-1) and respond to induction therapy have a chance of 5-year disease-free survival.
For localized forms of SCLC, chemotherapy (CT) is performed according to one of the above regimens (2-4 courses) in combination with radiation therapy (RT) to the area of the primary lesion, lung root and mediastinum with a total focal dose of 30-45 Gy (50-60 Gy according to 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 against the background of 1-2 courses of chemotherapy, or after assessing the effectiveness of treatment of two courses of chemotherapy.
For patients who have achieved complete remission, prophylactic irradiation of the brain is recommended at a total dose of 30 Gy due to the high risk (up to 70%) of metastasis to the brain.
The median survival of patients with localized SCLC using combination treatment is 16-24 months, with a 2-year survival rate of 40-50%, and a 5-year survival rate of 10%. In the group of patients who began treatment in good general condition, the possibility of achieving 5-year survival is 25%.
In such patients, the main treatment method is combination chemotherapy in the same regimens, and radiation is carried out only for 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 with complete tumor regression is significantly higher than with partial regression, and approaches the survival rate of patients with localized SCLC.
Table No. 1.
Schemes of modern combination chemotherapy for SCLC
| Drugs | Chemotherapy regimen | Interval between courses |
| EP Cisplatin Etoposide | 80 mg/m2 intravenously on day 1 120 mg/m2 intravenously on days 1, 2, 3 | Once every 3 weeks |
| CDE Cyclophosphamide Doxorubicin Etoposide | 1000 mg/m2 intravenously on day 1 45 mg/m2 intravenously on day 1 100 mg/m2 intravenously on days 1, 2, 3 or days 1, 3, 5 | Once every 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 | Once every 3 weeks |
| AVP Nimustine (CCNU) Etoposide Cisplatin | 2-3 mg/kg intravenously on day 1 100 mg/m2 intravenously on days 4,5,6 40 mg/m2 intravenously on days 1,2,3 | Once every 4-6 weeks |
| CODE Cisplatin Vincristine Doxorubicin Etoposide | 25 mg/m2 intravenously on day 1 1 mg/m2 intravenously on day 1 40 mg/m2 intravenously on day 1 80 mg/m2 intravenously 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 | Once every 3-4 weeks |
| TP Docetaxel Cisplatin | 75 mg/m2 intravenously on day 1 75 mg/m2 intravenously on day 1 | Once every 3 weeks |
| IP Irinotecan Cisplatin | 60 mg/m2 intravenously on days 1, 8, 15 60 mg/m2 intravenously on day 1 | Once every 3 weeks |
| G.P. Gemcitabine Cisplatin | 1000 mg/m2 intravenously on days 1.8 70 mg/m2 intravenously on day 1 | Once every 3 weeks |
For metastatic lesions bone marrow, distant lymph nodes, with metastatic pleurisy, the main treatment method is chemotherapy. 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). For metastatic lesions of the bones, brain, and adrenal glands, radiation therapy is the method of choice. For brain metastases, radiation therapy at a total focal dose (TLD) of 30 Gy produces a clinical effect in 70% of patients, and in half of them complete regression of the tumor is recorded according to CT data. Recently, reports have appeared about the possibility of using systemic chemotherapy for brain metastases. In table Figure 2 presents modern treatment tactics for various forms of SCLC.
Despite the high sensitivity to chemotherapy and radiation therapy for SCLC, this disease has a high rate of relapses; 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 location of metastatic foci.
It is customary to distinguish between patients with sensitive relapse of SCLC, i.e. who had a history of complete or partial response to first-line chemotherapy and progression in at least 3 months after completion of induction chemotherapy. In this case, it is possible to reuse the treatment regimen against which the effect was detected. There are patients with refractory relapse, i.e. when disease progression is observed during the first line of chemotherapy or in less than 3 months 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 after diagnosis of relapse does not exceed 3-4 months. In the presence of a refractory relapse, it is advisable to use previously unused cytostatics and/or their combinations.
Recently, new drugs have been studied and already used in the treatment of SCLC, these include gemcitabine, topotecan, vinorelbine, irinotecan, taxanes, as well as targeted drugs.
Gemcitabine. Gemcitabine is an analogue of deoxytidine and belongs to the 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 overall effectiveness level is 13%. Therefore, combination chemotherapy regimens including gemcitabine began to be studied. In an Italian study, treatment was carried out using the PEG regimen (gemcitabine, cisplatin, etoposide), with an objective efficacy rate of 72%, but high toxicity was noted. The London Lung Group published data from a randomized phase III trial directly comparing two treatment regimens: GC (gemcitabine + cisplatin) and PE. No differences in median survival were obtained, also noted here high level toxicity of the GC regimen.
Topotecan. Topotecan is a water-soluble drug that is a semi-synthetic analogue of camptothecin; it does not have 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 good tolerability of topotecan, characterized by controlled non-cumulative myelosuppression, a low level of non-hematological toxicity and a significant reduction clinical manifestations diseases. The use of topotecan in second-line treatment of SCLC is approved in approximately 40 countries, including the USA and Switzerland.
Vinorelbine. Vinorelbine is a semi-synthetic vinca alkaloid that is involved in preventing the depolymerization of tubulin. 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 low level toxicity. In the work of 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 regimen actively works 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 No. 2.
Modern tactics of treatment of SCLC
Irinotecan. Based on the results of a phase II study Japan Clinical Oncology Group started a randomized phase III trial JCOG -9511 for a direct comparison of two chemotherapy regimens: cisplatin + irinotecan ( P.I. ) and cisplatin + etoposide (PE) in previously untreated patients with SCLC. In the first combination, the dose of irinotecan was 60 mg/m2 in 1, 8 1st and 15th days, cisplatin - 60 mg/m2 on day 1 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 course of chemotherapy. It was planned to include 230 patients in the work, however, recruitment was stopped after a preliminary analysis of the results obtained ( n =154), since a significant increase in survival rate was detected in the group receiving treatment according to the regimen P.I. (median survival rate is 12.8 vs 9.4 months, respectively). However, it should be noted that only 29% of patients randomized to the P.I. , were able to get required dose drugs. According to this study, the pattern P.I. has been recognized in Japan as the standard of care for the treatment of localized SCLC. Due to the small number of patients, the data from this work needed to be confirmed.
Therefore in North America research was started III phases Taking into account the already available results, the doses of the drugs were reduced. In the scheme P.I. the dose of cisplatin was 30 mg/m 2 in 1 th day, irinotecan- 65 mg/m2 in 1st and 8th th days of a 3-week cycle. Regarding toxicity, grade IV diarrhea has not been reported, and preliminary efficacy data are awaited.
Taxanes. In the work of J. E. Smyth et al. the effectiveness of docetaxel was studied 100 mg/m2 in monotherapy in previously treated patients ( n =28), objective effectiveness was 25% [ 32 ].
In the ECOG study included 36 previously untreated patients with SCLC who received paclitaxel 250 mg/m 2 as a 24-hour infusion every 3 weeks. At the same time, the level of partial regression was 30%, at 56 In % of cases, grade IV leukopenia was recorded. However, interest in this cytostatic did not wane, and therefore in the USA it was started Intergroup Study , where the combination of paclitaxel with etoposide and cisplatin (TER) or carboplatin - (TEC) was studied. In the first group, chemotherapy was carried out according to the TEP regimen (paclitaxel 175 mg/m 2 in 1 day 1, etoposide 80 mg/m 2 in 1 - 3 days and cisplatin 80 mg/m 2 in 1 th day, while prerequisite was the introduction of colony-stimulating factors from days 4 to 14), in the PE regimen the drug doses were identical. A higher rate of toxicity was observed in the TEP group, unfortunately, no difference in median survival was obtained ( 10.4 versus 9.9 months).
M. Reck et al. presented data from a randomized trial III phase, in which the combination of TEC (paclitaxel 175 mg/m2) was studied in one group 2 on day 4, etoposide in 1 - 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 carboplatin AUC 5 on the 4th day), in another group - CEV (vincristine 2 mg in the 1st and 8 days, etoposide from days 1 to 3 at a dose of 159 mg/m 2 and 125 mg/m2 patients with stage I-ShV and stage IV and carboplatin AUC 5 on the 1st day). The median overall survival was 12.7 versus 10.9 months, respectively, however, the differences obtained were not significant (p = 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 SCLC therapy, new areas of drug treatment are being explored, tending to move from nonspecific drugs to so-called targeted therapy aimed at specific genes, receptors, and enzymes. In the coming years, it is the nature of molecular genetic disorders that will determine the choice drug regimens treatment in patients with SCLC.
Targeted therapy for aHmu-CD56. Small cell lung cancer cells are known to express CD 56. It is expressed by peripheral nerve endings, neuroendocrine tissues, and myocardium. To suppress expression CD 56 conjugated monoclonal antibodies were obtained N 901-bR . Patients took part in phase I of the study ( n = 21 ) with relapsed SCLC, they received an infusion of the drug for 7 days. In one case, partial regression of the tumor was recorded, the duration of which was 3 months. In progress British Biotech (Phase I) studied monoclonal antibodies mAb , which are conjugated into a toxin DM 1.DM 1 inhibits the polymerization of tubulin and microtubules, leading to cell death. Research in this area is ongoing.
Thalidomide. There is an opinion 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 an anti-insomnia drug, but 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 a phase II study, 26 patients with previously untreated SCLC underwent 6 courses of standard chemotherapy according to the PE regimen, and then for 2 years they received treatment with thalidomide(100 mg per day) with minimal toxicity. CR was registered in 2 patients, PR in 13, median survival was 10 months, 1-year survival was 42%. Taking into account the promising results obtained, it was decided to begin research III phases of the thalidomide study.
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 metalloproteinase inhibitors have already been synthesized and tested for small cell lung cancer, such as marimastat ( British Biotech) and BAY 12-9566 (Bayer).
IN large study The study of marimastat involved more than 500 patients with localized and disseminated forms of small cell lung cancer; after chemotherapy or chemoradiotherapy, one group of patients was prescribed marimastat (10 mg 2 times a day), the other - placebo. It was not possible to achieve an increase in survival rate. In the work of studying BAY 12-9566 in the study group showed a decrease in survival, so studies of metalloproteinase inhibitors in SCLC were stopped.
Also, in SCLC, drugs were studied,receptor tyrosine kinase inhibitors (gefitinib, imatinib). Only in the study of imatinib (Gleevec) promising results were obtained, and therefore work in this direction continues.
Thus, in conclusion, it should be emphasized once again that research is currently underway on new therapies for SCLC. On the one hand, new regimens and combinations with lower levels of toxicity and greater efficiency 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 some studies that include 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 a disease such as small cell lung cancer.
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