Targeted therapy for metastatic kidney cancer: how to achieve optimal clinical results? Russian International Symposium on Kidney Cancer

Active Surveillance

Active surveillance—monitoring the tumor with regular diagnostic tests and clinic visits.
It is effective in older patients and patients who have a small kidney tumor and other serious disease (heart, lung, chronic kidney disease) that interferes with cancer treatment or increases the risk of complications associated with it. For some patients with kidney cancer, active surveillance is used as long as they have minimal symptoms (or no symptoms at all), even if the cancer has spread to other parts of the body. Progression of the disease and deterioration of the patient’s condition is a reason to begin systemic therapy.

Surgical methods of treatment

Surgical treatment involves removing the tumor and some surrounding healthy tissue during surgery. If the cancer has not spread beyond the kidneys, the only treatment needed may be surgery to remove the tumor, part or all of the kidney, and possibly nearby tissue and lymph nodes.

Types of surgeries for kidney cancer

Radical nephrectomy. Usually performed when treating a large tumor, when there is little healthy kidney tissue left: the tumor, the affected organ and surrounding tissue are removed. If the disease affects nearby tissues and surrounding lymph nodes, radical nephrectomy and lymph node removal are performed. If the cancer has spread to the adrenal gland or nearby blood vessels, the surgeon may remove the adrenal gland (adrenalectomy) and parts of the blood vessels. Sometimes a kidney tumor grows directly inside the renal vein, and on the way to the heart, the tumor thrombus can grow into the vena cava. In this case, complex cardiovascular surgical interventions are necessary to safely remove all tumor changes.

Partial nephrectomy. Surgical removal of the tumor and part of healthy kidney tissue. This type of surgery preserves kidney function and reduces the risk of developing chronic kidney disease after surgery. Studies have shown that partial nephrectomy is effective for T1 tumors in all cases where surgery is possible.

Laparoscopic and robotic surgery (minimally invasive surgery). During laparoscopic surgery, organs are accessed through several small punctures in the abdominal wall. Through these punctures, the surgeon inserts laparoscopic instruments to completely remove the kidney or perform a partial nephrectomy. Sometimes the surgeon may use robotic instruments during surgery. Robotic surgery may take longer but is less traumatic. Laparoscopic and robotic approaches require special training. It is important to discuss the potential benefits and risks of such procedures with your surgeon in advance and to be sure that the surgical team has experience in performing them.

Non-surgical treatment of tumors

Sometimes surgical treatment is not indicated due to the characteristics of the tumor or the patient's general health. In such cases, the following manipulations may be recommended:

Radiofrequency ablation (RFA). Removal of pathologically altered tissues by burning with an electric current of a certain frequency. The procedure is performed by an interventional radiologist or urologist. The patient is sedated and given local anesthesia for pain relief.

Cryoablation (cryotherapy or cryosurgery). Freezing cancer cells using a metal probe that is placed into the tumor tissue through a small incision. Computed tomography and ultrasound are used to guide the probe. The procedure requires general anesthesia for several hours and is performed by an interventional radiologist. Some surgeons combine cryoablation with laparoscopic tumor removal, although there have been no full-scale studies on this topic, and accordingly, there is no complete and reliable data proving the effectiveness of this technique.

Systemic therapy

Systemic therapy is the use of drugs to kill cancer cells. Medicines taken orally or intravenously travel through the bloodstream throughout the body and affect cancer cells. Systemic therapy is usually prescribed by an oncologist, a doctor who specializes in treating cancer with drugs.

Types of systemic therapy for the treatment of kidney cancer: targeted therapy, immunotherapy, chemotherapy. The patient may receive one type of systemic therapy or a combination of medications. Systemic therapy drugs may also be used as part of treatment, which includes surgery and/or radiation therapy.

Targeted therapy

Targeted therapy is treatment aimed at specific “targets” in the tumor: genes, proteins and cell membrane receptors that promote the growth and survival of the cancer cell. This type of treatment blocks the growth and spread of cancer cells while causing minimal damage to healthy cells.

Types of targeted therapy for kidney cancer:

Antiangiogenic therapy . This type of treatment aims to stop angiogenesis, the process of creating new blood vessels. Most kidney cancer cells have mutations in the VHL gene, which cause the cancer to produce large amounts of a certain protein known as vascular endothelial growth factor (VEGF). VEGF controls the formation of new blood vessels because the tumor needs nutrients supplied by the bloodstream to grow and spread. The goal of antiangiogenic therapy is to block vascular growth factor to starve the tumor. There are 2 ways to block VEGF: using VEGF receptor (VEGFR) inhibitors or using antibodies directed against these receptors.

It has been established that recombinant hyperchimeric humanized monoclonal antibodies (bevacizumab, Avastin) are capable of slowing tumor growth in patients with metastatic renal cell carcinoma. Bevacizumab in combination with interferon slows down both the growth and process of tumor metastasis.

Another way to block VEGF is with tyrosine kinase inhibitors (TKIs). Tyrosine kinase inhibitors used to treat clear cell RCC include axitinib (Inlyta), cabozantinib (Cabometic, Cometrik), pazopanib (Votrient), sorafenib (Nexavar), and sunitinib (Sutent). Common side effects of TKIs include diarrhea, high blood pressure, skin rash, and hand-foot syndrome.

mTOR inhibitors. The drugs everolimus (Afinitor) and temsirolimus (Torisel) target a specific protein called mTOR, which helps kidney cancer cells grow. Research shows that these medications slow the growth of kidney cancer.

Combination therapy. In 2021, the US Food and Drug Administration (FDA) approved 2 drug combinations for the first-line treatment of advanced renal cell carcinoma.

The first combination includes the antiangiogenic drug axitinib and the immune checkpoint inhibitor pembrolizumab (for more details, see the Immunotherapy section below). The second combination uses axitinib and the immune checkpoint inhibitor avelumab.

Pembrolizumab and avelumab target the PD-1 pathway, which activates the immune system to attack cancer cells. These treatment combinations work regardless of whether the tumor expresses the PD-L1 protein, so patients receiving these therapies are not tested for PD-L1 gene expression.

During a consultation with an oncologist at the Rassvet Clinic, you can discuss the possible side effects of a particular medication and receive recommendations on how to cope with them.

Immunotherapy

Immunotherapy (biological therapy) is designed to enhance the body's natural immune defenses in the fight against cancer.

Interleukin-2 (IL-2, Proleukin). A type of immunotherapy to treat advanced kidney cancer. It is a cytokine, a protein produced by white blood cells. It is used by the immune system, including to destroy tumor cells.

High doses of IL-2 can cause severe side effects - low blood pressure, damage to the lungs, kidneys, heart muscle, bleeding, chills and fever, so in some cases it is advisable to treat in a hospital. Only centers with such experience should recommend high-dose IL-2 treatment for kidney cancer. Some centers use low doses of IL-2, which results in fewer side effects, but this treatment is less effective.

Alpha interferon. Alpha interferon is used to treat advanced kidney cancer. It has been found to be less effective than IL-2, but improves life expectancy in patients compared to an older treatment, the drug megestrol acetate (megaacetate).

Immune checkpoint inhibitors. The effectiveness of this type of immunotherapy for the treatment of kidney cancer continues to be studied. The FDA has approved a combination of two immune inhibitors, nivolumab (Opdivo) and ipilimumab (Yervoy), for the treatment of advanced renal cell carcinoma in previously untreated patients. Additional studies showed that nivolumab, given as a single dose intravenously every 2 weeks, was also effective in some previously treated patients. These patients lived longer than those who received targeted therapy with everolimus. Another approved combination includes the checkpoint inhibitors pembrolizumab or avelumab and the targeted drug axitinib as first-line treatment for patients with advanced renal cell carcinoma. Many clinical trials are currently underway to further investigate immune-based drugs in the treatment of kidney cancer.

Various types of immunotherapy may cause side effects. The most common side effects include skin reactions, flu-like symptoms, diarrhea, and weight loss.

Chemotherapy

Chemotherapy is a drug treatment that targets cancer cells. Chemotherapy drugs block the ability of cancer cells to divide and form more, which leads to slower growth of the tumor and its death.

Chemotherapy drugs are used in cycles at regular intervals. Typically, days of injecting or taking medications are followed by rest days. Thanks to such breaks, the body has time to recover. The days of using the drug and the days of rest constitute one cycle.

A combination of several chemotherapy drugs, including methods of administration and cycle length, is called a chemotherapy regimen.

Although chemotherapy has been successfully used to treat many types of cancer, most kidney cancers are resistant to chemotherapy. Research into new drugs and new drug combinations continues. In some patients, combining gemcitabine (Gemzar) with capecitabine (Xeloda) or 5-fluorouracil can temporarily shrink tumors.

It is important to remember that transitional cell carcinoma (urothelial) and Wilms tumor respond more effectively to chemotherapy.

Side effects of chemotherapy depend on the patient's general condition and the dose used, and may include weakness, nausea and vomiting, hair loss, loss of appetite and diarrhea. These side effects usually go away after treatment ends.

More details

Chemotherapy

First-line targeted therapy for kidney cancer

Basically, these types of drugs are used to reduce or control the course of the disease in case of widespread tumor process. Based on research and reviews, targeted therapy for kidney cancer stops or slows the progression of the disease for several months and sometimes years.

Medicines are usually taken as long as they control the disease. The patient meets with the doctor every 4-6 weeks and also has blood tests. Scans are performed every three months to determine whether the treatment is effective.

Let's consider targeted therapy regimens for kidney cancer. Sunitinib (Sutent) is generally recommended first for secondary lesions. Another common drug is Pazopanib. These drugs block growth signals in cancer cells and are called tyrosine kinase inhibitors. Sorafenib (Nexavar) is also prescribed in some cases.

Sunitinib

Sunitinib has another name - sutent. It is used at stages 3 or 4 of the disease. Taken in capsules daily for 4 weeks followed by a break of 2 weeks.

This drug belongs to the group of tyrosine kinase inhibitors. It blocks intracellular proteins called tyrosine kinases in tumor cells, which provide signals for growth and division and connect cells to the nucleus and cellular structures. In addition, sutent interferes with blood supply, depriving pathological cells of nutrients and oxygen.

Possible adverse effects include fatigue, increased risk of infection due to low white blood cell counts, anemia, changes in taste, diarrhea, skin rash and itching, palmoplantar keratoderma, and hypertension. Sunitinib may worsen the functioning of the thyroid gland, for this reason the patient has regular blood tests to check this.

Pazopanib

Pazopanib is a cancer growth inhibitor; a doctor may recommend the drug as a primary treatment for advanced tumors and as a secondary treatment after the use of interferon or interleukin-2. It comes in tablets and is taken every day. Potential negative consequences of taking it include: diarrhea, palmoplantar keratoderma, rash and itching of the skin, increased fatigue, nausea.

Radiation therapy

Radiation therapy is the use of high-energy X-rays or other particles to destroy cancer cells.

Radiation therapy is not effective for the primary treatment of kidney cancer. It is only used if the patient cannot undergo surgery, usually to areas where the cancer has metastasized rather than to the area of ​​the primary tumor. This treatment is given to relieve symptoms such as bone pain due to metastatic disease.

Supportive (palliative) therapy

Palliative care is specialized medical care aimed at relieving pain and other symptoms of a serious illness. Palliative care specialists work with the patient, family, and other health care providers to provide an additional level of support that complements ongoing care.

When palliative care is used in conjunction with all other appropriate treatments, cancer patients feel better and live longer.

Palliative care at the Rassvet Clinic is provided by a team of doctors, nurses and other specially trained staff. Palliative care teams strive to improve the quality of life of people with cancer. This form of care is offered along with medical or other treatments.

Potential side effects of targeted therapy

Doctors at Asaf HaRofeh Hospital select treatment based on highly accurate genetic tests, minimizing the unwanted effects of treatment.

Numerous modern techniques are used to manage and control side effects to reduce or prevent them.

• Fatigue. Taking these medications causes significant fatigue, which interferes with daily activities and sleep. Possible causes: depression, loss of appetite, anemia, specific medications, low thyroid hormone levels, accumulation of toxic waste due to treatment and death of pathological cells.
• Diarrhea. Targeted therapy drugs often target cells in the gastrointestinal tract. Also, the type and dose of medications can increase the likelihood of this adverse event.
• Vomiting and nausea. These symptoms are usually noted in the first few hours after taking the medication and may persist throughout the day.
• Loss of appetite is observed during targeted therapy. Factors influencing this manifestation are vomiting, fatigue, nausea, and accumulation of waste in the body.
• Hypertension – High blood pressure can be caused by targeted therapy. Doctors check your blood pressure regularly during treatment. If necessary, medications are prescribed to lower it.
• Some people may experience shortness of breath during targeted therapy for kidney cancer.
• An inflammatory process in the oral cavity occurs, which is caused by taking sunitinib. Occurs within one to two weeks after the start of therapy. The patient is counseled about careful and regular oral care, which can help prevent inflammation and reduce the chance of infection. Analgesics are prescribed to relieve pain.
• Targeted therapy for kidney cancer can provoke hand-foot syndrome. Its symptoms include pain, swelling, redness, tingling, burning and peeling of the skin on the arms or legs or on both extremities.
• Changes in the skin under the influence of treatment include the following symptoms: redness, dryness, rash, itching, peeling, formation of blisters and calluses, acne, changes in nails.
• Digestive problems may occur under the influence of targeted therapy for kidney cancer: heartburn, gas formation, bloating, stomach pain. Over-the-counter medications taken to improve digestion, such as ranitidine or omeprazole, may interfere with some targeted therapies. It is important to talk to your doctor before taking these medications.
• Some targeted drugs can reduce the amount of thyroid-stimulating hormone (TSH) produced by the pituitary gland. This hormone signals the thyroid gland to produce hormones that control metabolism. Signs and symptoms of an underactive thyroid include: fatigue, weakness, cold intolerance, muscle pain and cramps.
• During targeted therapy for kidney cancer, regular blood tests are done to check for low TSH. If necessary, medications are prescribed to correct its amount.
• Heart problems. Some targeted drugs can cause heart damage. An ECG and other tests are performed to check heart function before starting treatment, especially if you have a history of heart disease.
• Changes in the biochemical blood test are possible under the influence of this therapy: high sugar levels, increased cholesterol levels, decreased phosphate levels in the blood (causing weakness, trembling, confusion).
• Bone marrow suppression is a condition in which the number of blood cells - white blood cells, platelets or red blood cells - decreases, which increases the risk of infection, bruising and bleeding, and anemia.
• Interstitial pneumonitis is a type of pneumonia that develops in the connective tissue of the lung. Everolimus may cause non-infectious pneumonia.
• Hair thinning or hair loss is often caused by taking the drugs sorafenib and pazopanib. Hair follicles are vulnerable to targeted therapy for kidney cancer because they grow quickly. The extent and duration of the side effect is unpredictable, but hair usually grows back after treatment.

Metastatic kidney cancer

Metastatic cancer is a malignant tumor that spreads to other organs and tissues through metastases.

Kidney cancer most often metastasizes to the lungs, but can also spread to the lymph nodes, bones, liver, brain, skin and other areas of the body. This is a systemic disease that requires systemic therapy - targeted or immunotherapy. Sometimes, in the presence of metastases, the tumor-affected kidney is removed (cytoreductive nephrectomy). This surgery prevents pain and bleeding during systemic treatment. If kidney cancer has spread to one organ (for example, a single metastasis in the lung), surgical removal of the lesion (metastasectomy) may be performed. This operation helps to increase life expectancy in some patients. If the cancer has spread to many organs or tissues outside the kidney, it is more difficult to treat. Surgery does not help in this case; instead, systemic therapy is performed.

The most effective treatments for metastatic kidney cancer today are combinations of immune drugs that activate the immune system to destroy cancer cells. They prolong life compared to standard treatment. Palliative medicine is also important to relieve symptoms and side effects.

In what cases is targeted therapy prescribed for kidney cancer?

The main indication for the use of targeted drugs for malignant kidney tumors is the ineffectiveness of chemotherapy . Targeted therapy is often used for advanced malignant tumors in advanced stages. It is not intended to cure cancer, but it can reduce the size of the tumor and slow its growth - this helps to increase the patient's life expectancy.

Another area of ​​application of targeted drugs for kidney cancer is as adjuvant therapy after surgical treatment. A drug called sunitinib helps prevent relapse.

Targeted drugs for kidney cancer are usually prescribed as monotherapy . Some of them need to be taken in tablets, others are administered intravenously. If the drug does not work, it is discontinued and another one is prescribed.

Targeted therapy for malignant kidney tumors has not yet been studied enough; it is impossible to say which medicine will work best in this case, whether they should be combined to enhance the effect, and if so, how to do it correctly. These nuances remain to be clarified through research.

Write to an oncologist

Remission and relapse

Remission is an improvement in the patient’s condition after treatment, characterized by the cessation of the manifestation of the disease: the absence of symptoms of tumor lesions and signs of cancer during examination.

Remission can be temporary or permanent. This uncertainty causes many patients to worry that the cancer will return (recurrence).

Understanding the risk of relapse and possible treatment options helps the patient feel more confident.

At a consultation with an oncologist at the Rassvet clinic, you can receive the necessary information about the prognosis of your disease, this will help you more effectively cope with the fear of the disease returning.

Cancer can recur in the area of ​​the original tumor (local recurrence), in an area close to the original tumor (regional recurrence), or in another area (distant recurrence). If the patient has previously had a partial kidney removed, a new tumor may form in the same kidney. Recurrent tumors can be removed by partial nephrectomy or radical nephrectomy.

If there is a relapse, a new round of examinations begins to learn as much as possible about the spread of the cancer. Often the treatment plan includes the methods described above: surgery, targeted therapy, or immunotherapy. But they can be used in a different combination or in a different mode. Regardless of the treatment plan, palliative care will be important to relieve symptoms and side effects.

People with recurrent cancer often experience negative emotions, mistrust, or fear. At the Rassvet Clinic, you can discuss these problems with a psychologist and learn to cope with them better.

Patient support

Also, when fighting cancer, one of the key tasks of the doctor and the patient himself is the formation of a positive psycho-emotional background. Regardless of which method of treatment is chosen, be it targeted therapy or irradiation of cancer cells, it is unacceptable to expect a negative result.

Qualified specialists help improve the mood and general well-being of patients in the following ways:

• prescribe medications that help cope with concomitant pathologies;
• antipsychotic drugs are administered;
• prescribe painkillers to relieve pain if necessary;
• establish control of resuscitators who constantly monitor homeostasis and other indicators of the body;
• prescribe physiotherapeutic procedures, etc.

In this case, the patient must constantly be in favorable conditions. No matter how effective targeted therapy is, a positive attitude makes a significant contribution to the final result of the treatment process.

Observation after treatment

Monitoring of patients with cancer continues after completion of active treatment. This may include regular physical examinations and medical tests, including to rule out recurrence.

Recommendations for monitoring a patient depend on several factors, including the type and stage of cancer and the type of treatment received. Patients who have undergone surgery for kidney cancer often need to have their kidney function monitored for the rest of their lives.

The team of doctors at the oncology department of the Rassvet Clinic continues to monitor the patient after treatment. We not only screen for relapse, but also help manage side effects and monitor your overall health.

Experience with the use of targeted drugs in patients with metastatic kidney cancer

The article presents the experience of treating patients with metastatic kidney cancer using targeted therapy. It is proposed to determine the treatment strategy, taking into account not only recommendations for the order of prescription of targeted drugs depending on the prognosis of the disease, but also the individual reactions of the patient, as well as the effectiveness of the drugs in each specific case.

Rice. 1. Multiple metastases to the lungs, metastasis to the only left kidney

Rice. 2. Metastasis to soft tissues

Treatment of patients with kidney cancer is one of the pressing problems of urological oncology. Kidney cancer occupies a leading place in the structure of oncological diseases, and in terms of the rate of increase in incidence it ranks second among oncological diseases. In Russia in 2011, about 20 thousand patients with malignant kidney tumors were identified [1].

The main method of treating kidney cancer remains surgical, but, according to statistics, a large number of patients who have undergone radical surgery are subsequently diagnosed with disease progression. In recent years, the use of targeted drugs has made it possible to achieve unconditional success in the treatment of patients with metastatic kidney cancer. The rapidly developing practice of treatment with targeted drugs gives hope to severe patients with metastatic kidney cancer to prolong life and improve disease control.

Despite the fact that there are already recommendations for the sequential prescription of targeted drugs taking into account the prognosis of the disease, in a large number of cases it is necessary to select therapy individually, assessing the effectiveness of the drug and the response of each patient. Let us illustrate these statements with specific clinical examples.

Clinical case 1

This clinical case represents, in our opinion, a typical example of the development of the disease in patients with kidney cancer.

Patient A., diagnosis: “cancer of the right kidney T3N0M0.”

The diagnosis was made in November 2011 during an examination regarding complaints of pain in the right hypochondrium. Computed tomography (CT) showed a tumor in the right kidney measuring 90 × 70 mm with invasion of the renal capsule. Radical nephrectomy on the right was performed on February 14, 2012. Histological conclusion No. 7417-33/12-10: renal cell clear cell carcinoma.

In October 2012, a CT scan revealed progression of the disease: metastases to the lungs and intrathoracic lymph nodes. Status on the Eastern Cooperative Oncology Group (ECOG) scale for assessing the general condition of a cancer patient is 0–1, the prognosis is considered unfavorable. Taking into account the histological type of the tumor, the patient was prescribed targeted therapy with sunitinib 50 mg/day from November 28, 2012. He tolerated the treatment satisfactorily. Side effects were moderate (grade 1), mainly skin toxicity and heartburn. The patient received antacid therapy with a positive effect. To correct skin reactions, moisturizing creams were prescribed. No dose reduction was required. The patient continued treatment.

A follow-up examination (CT scan of the chest and abdominal cavity) two months later showed a decrease in the size of the lesions in the lungs. No new foci were identified. This was considered a partial response to the therapy.

Subsequent follow-up examinations revealed no signs of disease progression. The patient is currently receiving therapy with sunitinib (for 12 months), tolerability is assessed as good. Taking into account the good clinical effect of the therapy and moderate toxic manifestations, it was decided to continue therapy with sunitinib at a dose of 50 mg/day.

Clinical case 2

Patient T., born in 1950 Right kidney cancer T2N0M0, diagnosed in 2002.

On May 30, 2002, radical nephrectomy was performed on the right. Histological conclusion: clear cell renal cell carcinoma. The postoperative period proceeded without complications. Subsequently, dynamic monitoring of the patient was carried out.

In April 2010, the patient noted the appearance of bloody discharge from the nasal cavity. Upon examination by an otorhinolaryngologist in the clinic, a tumor of the left half of the nasal cavity was suspected. The patient was admitted to the ENT department of the oncology hospital for morphological verification of the diagnosis. At the time of admission to the hospital, the patient had grade 1 anemia due to frequent nosebleeds. After repeated attempts to puncture the tumor on the left half of the nose, no histological material was obtained and it was not possible to establish the morphology of the tumor. Anemia continued to worsen (hemoglobin 92 g/l). The patient underwent anterior tamponade of the left half of the nasal cavity. According to CT data of the chest and abdominal cavity, multiple metastases to the lungs and a metastasis to the only left kidney were identified (Fig. 1).

The patient was discharged under the supervision of an oncologist at the place of residence with recommendations for symptomatic therapy. Despite the fact that no morphological material was obtained, a tumor in the nasal cavity, focal formations in the lungs and a tumor in the only left kidney were regarded as metastases of renal cell carcinoma. The only treatment option at that time in the oncology clinic was immunotherapy with interferon, which was prescribed to the patient at a dose of 6 million units 3 times a week subcutaneously.

The patient tolerated the treatment satisfactorily and noted a significant decrease in bloody discharge from the nasal cavity. The pain has decreased. There were no signs of enlarged tumor foci in the lungs and the only left kidney. However, the bleeding did not stop completely, which was accompanied by a decrease in hemoglobin level to 87 g/l. To correct anemia, erythropoietin and iron supplements were prescribed, and hemostatic therapy was continued. This had a positive effect: the hemoglobin level rose to 95 g/l.

In March 2011, the patient was urgently hospitalized with profuse nosebleeds. For health reasons, on March 5, 2011, ligation of the external carotid artery on the left was performed. The bleeding has stopped. At the time of hospitalization, interferon treatment had been continued for 10 months.

On March 24, 2011, electrical resection of the tumor in the left half of the nasal cavity was performed. Histological examination revealed a chemodectoma with superficial necrosis of the neoplasm. The specimens were sent for immunohistochemical examination, the results of which established that the tumor belonged to clear cell renal cell carcinoma. Taking into account histological data, the patient was prescribed targeted therapy with bevacizumab and interferon from July 2011. ECOG status – 0–1. He tolerated the treatment satisfactorily. Since the nosebleeds were stopped, the hemoglobin level increased to 132 g/l. Therapy continued for 5 months.

In November 2011, metastases were detected in the intrathoracic lymph nodes (according to CT scan of the chest). Metastases to the lungs and left kidney were without dynamics. A decision was made to change the targeted drug. In November 2011, therapy with sorafenib 800 mg/day was started. The patient tolerated the treatment satisfactorily for 4 months.

However, during a follow-up examination in February 2012, metastases were revealed in the tissue of the anterior wall of the abdominal cavity. The diagnosis was confirmed by ultrasound examination, and fine-needle puncture of these lesions was performed under ultrasound guidance (Fig. 2). Histological conclusion No. 3094-99: renal cell carcinoma. Sorafenib treatment was interrupted.

Due to family circumstances, the patient did not show up for a follow-up appointment immediately after receiving the puncture results. At the next visit in May 2012, a moderate growth of lesions in the soft tissues of the anterior wall of the abdominal cavity (according to ultrasound) and an increase in intrathoracic lymph nodes (according to CT of the chest) were revealed.

Considering the progression of the disease after two lines of targeted therapy, the patient was prescribed therapy with the mTOR inhibitor (mammalian target of rapamycin - the target of rapamycin in mammalian cells) everolimus 10 mg/day from May 2012. The patient tolerated the treatment satisfactorily. However, during the next examination in September 2012, progression of the disease was revealed: the appearance of a new lesion and an increase in previously identified metastatic foci in the soft tissues of the anterior abdominal wall and metastasis in the only left kidney. Thus, everolimus therapy lasted about 4 months and was interrupted due to disease progression. The patient's general condition remained satisfactory (ECOG score – 0).

Taking into account the progression of the disease and the satisfactory general condition of the patient, it was decided to continue targeted therapy. Sunitinib was chosen taking into account the widest spectrum of action of the drug on tyrosine kinases, as well as on all known receptors for platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), involved in the process of tumor growth, pathological angiogenesis and metastasis [2–4].

Since September 2012, the patient began taking sunitinib at a dose of 50 mg/day. The treatment was tolerated satisfactorily with moderate manifestations of arterial hypertension.

During a follow-up examination of the patient in November 2012, positive dynamics were noted: the size of the lesions in the soft tissues and the lesion in the only left kidney decreased. A chest CT scan showed shrinkage of the intrathoracic lymph nodes, which was considered a partial response. Taking into account these data and good tolerability of the drug, treatment was continued at the same dose.

During a follow-up examination in January 2013, stabilization of the disease was revealed, and it was decided to continue therapy with sunitinib 50 mg/day. Currently, the patient continues to take sunitinib 50 mg/day with positive dynamics and satisfactory tolerability of treatment for 14 months.

This clinical example confirms the fact that even taking into account prognostic factors, it is very difficult to predict the response of a particular patient to a drug. Fortunately, the arsenal of targeted drugs currently makes it possible to quite effectively treat patients with metastatic kidney cancer, achieving long-term stabilization.

Conclusion

It should be emphasized that each patient with metastatic kidney cancer needs an individual approach; in addition, it is necessary to carefully monitor the progress of treatment with targeted drugs. Despite the availability of recommendations for the use of targeted therapy in such patients, taking into account prognostic factors, real clinical situations do not always allow following standard recommendations. The experience of the doctor conducting targeted therapy and his interaction with specialists examining the patient within control periods during therapy are of decisive importance, subject to strict adherence to these examination periods, which is especially important for domestic clinical practice.