Chemotherapy is often used to treat cancer. Chemical therapy involves the treatment of kidney cancer with antitumor medications, the active substance of which is capable of completely eliminating cancer cells and their formations. The powerful effect of therapy allows it to be used in later stages of cancer. The principle of chemotherapy at the last stage is the elimination of cancer cells and metastases that did not go away after surgery. In this article we will tell you how effective chemotherapy is for kidney cancer, and also analyze its principle of action.
What is immunotherapy for kidney cancer?
Kidney cancer
is one of the types of cancer that responds well to immunotherapy drugs. The goal of immunotherapy (sometimes called biological therapy) is to mobilize the patient's immune system to fight cancer cells.
Interesting fact.
The foundations of immunotherapy in oncology were laid in the second half of the 19th century, when the American surgeon William Coley injected inactivated bacteria into sarcoma tissue and tumors. Only years later was it possible to explain the miraculous effect by an immune response to bacterial fragments that destroyed tumor cells.
Today, a number of targeted and immunotherapy drugs have been approved in our country for the treatment of kidney cancer, including immune checkpoint inhibitors (nivolumab). Highly toxic chemotherapy is gradually becoming a backup option, which is used only when the possibilities of immunotherapy are completely exhausted.
Alternative Methods
These include proper nutrition, a healthy lifestyle, folk remedies, herbal medicine, and aerotherapy.
Food
Products that increase immunity in oncology are:
- honey,
- beets, broccoli, tomatoes,
- onion, garlic, red pepper.
Their use helps influence the process of cellular mutations.
Those that kill cancer cells are:
- nuts, pumpkin and sunflower seeds,
- seafood rich in Omega 3,
- milk, its derivatives,
- turmeric, avocado, blueberries, cranberries, beans.
Aerotherapy
Air treatment is indicated for various forms of skin cancer. Immunotherapy for melanoma includes air baths as an element of strengthening the body's defenses to resist the disease. Air procedures are combined with inhalation of healing aromas saturated with ether vapors.
Long-term round-the-clock aerotherapy is carried out at resorts, the sea coast, and in pine forests. There are specially created pavilions where the patient inhales ion-saturated air, saturated with salts and phytoncides. The use of aerotherapy is relevant for oncology of the respiratory organs, ENT, and dermatological pathologies.
Phytotherapy
Oncology immunotherapy strengthens the defense mechanism, and medicinal plants help in this. Decoctions, infusions, lotions reduce the symptoms of the disease and have a positive effect on the production of immune cells. Recognized immunomodulators are:
- eleutherococcus, sweet clover, calendula,
- ginseng, Rhodiola rosea, Schisandra chinensis,
- tartar, sedum, burdock,
- mallow, immortelle, barberry,
- marsh calamus, marshmallow.
Leaves, inflorescences and roots contain substances that affect the processes occurring in the cells of the body. Therefore, doctors recommend products prepared on the basis of folk recipes as an additional link in cancer immunotherapy.
How does immunotherapy work?
Modern immunotherapies include cytokines (alpha-interferon, interleukin-2), as well as immune checkpoint inhibitors (nivolumab, pembrolizumab). Let's look at each group in more detail.
Cytokines
A group of cytokines are analogues of natural proteins that activate the immune system.
For immunotherapy of kidney cancer, interleukin-2 (IL-2) or alpha-interferon is mainly prescribed. The response rate to cytokines is low. Interleukin-2 (IL-2)
In the past, IL-2 served as a first-line treatment for advanced kidney cancer.
Interleukin-2 remains relevant, but serious adverse reactions limit its use. Foreign oncologists prefer to prescribe IL-2 to relatively healthy and strong patients or to those who respond poorly to targeted drugs.
Although few patients respond to interleukin-2, this therapy for kidney cancer may provide promising long-term results. Today, scientists are actively looking for markers that can predict the effectiveness of IL-2 in a particular patient.
The use of high doses of interleukin-2 gives the greatest chance of defeating cancer, but the toxicity of IL-2 is directly dependent on the dose. Side effects do not allow using all the capabilities of interleukin in weakened, seriously ill people.
Side effects of interleukin-2:
• Mental changes • Low blood pressure • Excessive weakness and fatigue • Intestinal bleeding • Diarrhea and abdominal pain • High temperature • Flu-like symptoms • Fluid accumulation in the lungs • Rapid heartbeat • Myocardial infarction • Kidney damage
Adverse reactions can be fatal in rare cases. To recognize them in time, continuous qualified observation and analysis is required. The drug should be prescribed only by oncologists with relevant experience.
Alpha interferon
Interferon compares favorably with IL-2 in its safety profile, but in monotherapy it is inferior to interleukin in effectiveness.
For kidney cancer, alpha interferon is usually used in combination with the targeted drug bevacizumab (Avastin). It is administered subcutaneously three times a week. Side effects resemble a cold: chills, aches, fever, weakness, nausea.
With long-term treatment, interferon alpha can lead to weight loss, chronic fatigue, and depression.
Cost of immunotherapy course
Oncological immunotherapy is considered an expensive treatment, since it is carried out with substances obtained using complex biotechnologies. The latest developments in genetics and molecular chemistry are used. The drugs are obtained in a laboratory, they are applicable for a specific patient, against a specific cancer. The program varies depending on the stage of the disease, the degree of metastasis, and tumor growth. Oncology requires a complex treatment algorithm, various specialists are involved in the process, and expensive diagnostics are needed. This affects the price of a course of immunotherapy.
Immune checkpoint inhibitors
For the existence of the human body, it is important to protect healthy cells from its own immune system.
Over the course of evolution, lymphocytes have acquired “checkpoints”—molecular switches that must be activated to initiate an immune response. Cancer cells often use checkpoints to trick the victim's immune system. New drugs - PD-1 and PD-L1 inhibitors - actually deprive them of this opportunity.
Nivolumab (Opdivo) is a prominent representative of PD-1 inhibitors. By blocking checkpoints on the surface of T lymphocytes, nivolumab enhances the immune response, slows tumor growth and prevents the occurrence of metastases. The drug may be prescribed to patients with kidney cancer that has resumed growth after treatment with other drugs. It is administered intravenously.
Other immune checkpoint inhibitors:
• atezolizumab (Tecentriq) • pembrolizumab (Keytruda) • durvalumab (Imfinzi)
Immunity restoration after treatment
Unlike immunotherapy, chemotherapy and radiation have a detrimental effect on the immune system. It must be restored with the help of strengthening vitamins, herbal medicine, and a healthy lifestyle. But it is not recommended to independently develop a program for restoring the body’s internal reserves; this is done in consultation with the attending physician.
The scheme of restoration measures for the immune system involves treatment with natural adaptogens and antioxidants. Additional therapy cannot be ignored. It protects a weakened body from internal and external factors that provoke the development of oncology.
Side effects of immune checkpoint inhibitors
Drugs in this group are well tolerated, and serious adverse reactions occur rarely.
Classic side effects include:
• Nausea • Weakness • Fatigue • Dry cough • Skin rash • Joint pain • Loss of appetite • Diarrhea • Constipation
Figuratively speaking, checkpoint inhibitors “break the brakes” on the patient’s immunity, so in some cases dangerous autoimmune processes develop. T lymphocytes attack healthy cells and organs of the host. Targets include the lungs, skin, intestines, liver (hepatitis), thyroid gland (thyroiditis), pituitary gland (hypophysitis) and the kidneys themselves.
For nivolumab itself, the incidence of treatment-related adverse reactions is independent of dose. The patterns and timing of immune-mediated reactions are relatively predictable; damage to the endocrine glands is observed earlier (3-4 months), damage to the digestive tract and kidneys – later (4-6 months after the start of immunotherapy).
It is very important to tell your doctor promptly about any side effects. In some cases, immunotherapy has to be discontinued. Your doctor may prescribe high doses of corticosteroids to suppress your immune system.
Indications for use
The drug is intended for the complex treatment of adult patients with the following diseases:
- acute viral hepatitis B in severe and moderate forms up to the fifth day of jaundice (ineffective in later periods of this period, not effective in the development of hepatic coma and cholestatic course of the pathology);
- acute protracted hepatitis B and C, as well as chronic active hepatitis B, C and D without symptoms of cirrhosis;
- mycoplasma, viral (adenoviral, influenza, enteroviral, mumps, herpetic), as well as viral-bacterial meningoencephalitis (most effective during the first 4 days of the disease);
- viral keratitis, conjunctivitis, keratouveitis, keratoconjunctivitis;
- Stage IV kidney cancer, hairy cell leukemia, malignant lymphomas of the skin (primary reticulosis, mycosis fungoides), Kaposi's sarcoma, squamous cell and basal cell skin cancer, chronic myeloid leukemia, keratoacanthoma, histiocytosis-X, essential thrombocytopenia, subleukemic myelosis;
- multiple sclerosis.
Reaferon-EC is used subconjunctivally, locally, under the lesion or directly into the lesion itself - intramuscularly.
Right before the procedure, the powder of one ampoule of the drug is dissolved in 1 ml of water for injection for intramuscular administration, or in 5 ml for local and subconjunctival use. The dissolution time of the powder is from 2 to 4 minutes; the resulting drug solution should be free of foreign inclusions and completely transparent.
Therapy of acute hepatitis B involves intramuscular injections of Reaferon-EC twice a day at a dose of 1,000,000 IU. Treatment is carried out for 5-6 days, after which the dose is reduced by half to 1,000,000 IU per day. At a reduced dose, therapy continues for another 5 days. After conducting control biochemical blood tests and if further necessary, the course of therapy can be continued for 14 days at a dose of 1,000,000 IU, administered 2 times every 7 days. The total dose of the course is 15000000-21000000 IU.
Acute hepatitis B and chronic hepatitis B in the active phase, passing without the addition of delta infection and symptoms of liver cirrhosis, require a dose of the drug of 1,000,000 IU and administered intramuscularly 2 times every 7 days for 30-60 days. If there is a negative effect from treatment, the course of therapy is extended to 90-180 days or 2-3 courses of 30-60 days are carried out with breaks from 30 days to six months.
Therapy for acute protracted and chronic active hepatitis C without symptoms of liver cirrhosis is carried out intramuscularly at a dose of 3,000,000 IU, administered 3 times every 7 days, the course of treatment is 6-8 months. It is possible to extend therapy up to 12 months if there is no positive effect from the treatment. A repeat course can be prescribed after 3-6 months.
The course of treatment for chronic active hepatitis D without symptoms of cirrhosis is 30 days and consists of two intramuscular injections per week at a dose of 500,000-1,000,000 IU. If necessary, a second course of therapy can be carried out after 1-6 months.
The dose of the drug for active chronic hepatitis B or D with symptoms of liver cirrhosis is 250,000-500,000 IU per day, administered intramuscularly for 30 days, 2 times a week. If symptoms of decompensation occur, repeat similar courses of treatment are prescribed with intervals of at least 60 days.
Treatment of kidney cancer begins with a daily dose of 3,000,000 IU, administered intramuscularly for 10 days. Repeated courses of therapy can be carried out while maintaining the previous dose with breaks of 3 weeks. As a rule, from 3 to 9 courses or more are carried out with a total dose of the drug from 120000000 IU to 300000000 IU and even more.
The daily intramuscular dose of Reaferon-EC for the treatment of hairy cell leukemia ranges from 3,000,000 to 6,000,000 IU, with a course of therapy of up to 2 months. Normalization of the hemogram makes it possible to reduce the daily dose of the drug to 1,000,000-2,000,000 IU. Maintenance therapy is carried out for 6-7 weeks at a dose of 3,000,000 IU, intramuscularly twice every 7 days. The total dose is 420000000-600000000 IU and even more.
Therapy of lymphoblastic leukemia in childhood patients, carried out in the remission phase (4-5 months) after inductive chemotherapy, is prescribed at a dose of 1,000,000 IU intramuscularly. Injections are given once every 7 days for 6 months, after which they switch to 1 injection every 2 weeks. The course of treatment is generally 2 years. At the same time, maintenance chemotherapy is recommended.
Chronic myeloid leukemia is treated at a dose of 3,000,000 IU, administered intramuscularly every day or in a double dose every other day. The duration of therapy ranges from 2.5 months to 6 months.
Intramuscular administration of Reaferon-EC is recommended for the treatment of histiocytosis-X, which is carried out at a daily dose of 3,000,000 IU for 30 days. It is possible to conduct repeated courses over 1-3 years with 1-2 month breaks.
To correct hyperthrombocytosis in essential thrombocytopenia and subleukemic myelosis, intramuscular injections of Reaferon-EC are prescribed in a daily dose of 1,000,000 IU. The course of therapy is 20 days.
For Kaposi's sarcoma and malignant lymphomas, the recommended intramuscular daily dose of the drug is 3,000,000 IU. Treatment is carried out for 10 days in combination with cytostatics (Cyclophosphamide, Prospidin) and glucocorticoids.
Therapy for reticulosarcomatosis and the tumor phase of mycosis fungoides is carried out in the form of intramuscular injections at a dose of 3,000,000 IU, alternating with intralesional injections at a dose of 2,000,000 IU. The course of therapy is 10 days. In patients with mycosis fungoides in the erythrodermic stage, an increase in temperature above 39 ° C, as well as an exacerbation of the procedure, the administration of the drug serves as a signal to stop treatment.
The daily dose of the drug for the treatment of juvenile respiratory papillomatosis of the larynx is 100,000-150,000 IU per kilogram of weight. This treatment is carried out for 45-50 days. Afterwards, they switch to administering a similar dose for one month, 3 times a week. Further two courses of therapy are carried out with a break of 2-6 months.
Pyramidal syndrome of multiple sclerosis can be treated at a dose of 1,000,000 IU intramuscularly 3 times a day. Cerebellar syndrome of multiple sclerosis - 1,000,000 IU intramuscularly 1-2 times a day. The course of therapy in both cases is 10 days, after which they switch to injections at the same dose once every 7 days for 5-6 months. The total dose of the drug varies from 50,000,000 to 60,000,000 IU.
Perifocal administration of the drug Reaferon-EC is recommended for the treatment of squamous cell carcinoma, basal cell carcinoma and keratoacanthoma. The drug is administered once a day directly under the lesion at a dose of 1,000,000 IU for 10 days daily. In case of severe inflammatory reactions at the injection site, injections are carried out after 1-2 days. If necessary, after completion of the course of treatment, cryodestruction is prescribed.
For keratoiridocyclitis and stromal keratitis, subconjunctival administration is recommended in a daily dose of 60,000 IU with a solution volume of 0.5 ml, every day or every other day. Injections are made under local anesthesia, which is used as a 0.5% solution of Dicaine. The full course of therapy ranges from 15 to 25 injections.
Local use of the drug solution is recommended for superficial keratitis and conjunctivitis. The procedure consists of applying 2 drops of solution to the conjunctiva of the affected eye, 6-8 times a day. As the inflammatory manifestations subside, the number of installations is reduced to 3-4 per day. The course of therapy is 14 days.
To prepare a locally used solution, dissolve the contents of one ampoule of Reaferon-EC in 5 ml of 0.9% sodium chloride solution. The prepared medicine can be stored for no more than 12 hours in the refrigerator at a temperature of 2-8 ° C.
If you follow all the above recommended doses of Reaferon-EC, an overdose is unlikely.
If you follow all the rules for storing, transporting and using the drug, reviews of its effectiveness in various diseases of adult patients and children are positive in 95% of cases. Adverse reactions are most often observed when storage temperatures are not observed.
The price of Reaferon in Russian pharmacies, depending on the dosage and number of ampoules, varies greatly. For example, you can purchase ampoules of 3,000,000 IU No. 5 for 1,200-1,500 rubles.
Upon admission to the clinic, a patient with a kidney tumor undergoes a general clinical examination, including computed tomograms, ultrasound, isotope and x-ray examinations, as a result of which the stage of the disease is established. Next, diagnostic angiography is performed and, in the case of satisfactory blood supply to the tumor node, embolization of the renal artery is carried out with avalon, a hemostatic sponge and metal spirals with the simultaneous introduction of 5-fluorouracil and interferon-alpha into it.
In the post-embolization period, after 2-3 days, they begin the administration of Roncoleukin (recombinant interleukin-2) at a dose of 500 thousand IU, alternating it with intramuscular administration of interferon-alpha at a dose of 3 million IU/m2. In the future, the patient undergoes a control examination every three months and if there are signs of disease progression or renal artery recanalization, the course of treatment is repeated. When regression of metastases is achieved and the tumor size decreases, the patient undergoes nephrectomy.
Example 1. Patient S. born in 1960 Case history No. 101. Admitted to the clinic for the first time on January 11, 1999. From the anamnesis it is known that on January 4, 1999, there was an episode of hematuria, and therefore he went to the clinic at his place of residence, where, according to an ultrasound examination, a tumor of the right kidney was detected, and therefore he was sent to the Central Scientific Research Institute of Radiological Research and Treatment for further examination and treatment.
Combination therapy: new research and drugs
The past decade has seen the emergence of an impressive arsenal of experimental drugs for the treatment of renal cell carcinoma.
Today, it is common to prescribe immunotherapy and targeted drugs sequentially. But companies in the US and other Western countries are conducting clinical trials of new combination therapy regimens. These efforts allow scientists to combine multiple, complementary drug mechanisms to overcome cancer resistance, restore functional immune control, and improve patient survival.
Unfortunately, immunotherapy for kidney cancer is just beginning to develop. Current results are far from optimal, so participation in clinical trials of new drugs and combinations is often a real chance of survival.
Examples of experimental combination therapy regimens
Immunotherapy + immunotherapy:
• Nivolumab (anti-PD-1) + ipilimumab (anti-CTLA-4) • Atezolizumab (anti-PD-L1) + varilimumab (anti-CD-27) • Pembrolizumab (anti-PD-1) + ipilimumab (anti-CTLA-4) • Pidilizumab (anti-PD-1) + tumor vaccine • Tremelimumab (anti-CTLA-4) + durvalumab (anti-PD-1)
Immunotherapy + targeted therapy:
• Pembrolizumab (anti-PD-1) + pazopanib (TKI) • Nivolumab (anti-PD-1) + bevacizumab (anti-VEGF) • Atezolizumab (anti-PD-L1) + bevacizumab (anti-VEGF) • Nivolumab (anti-VEGF) -PD-1) + multikinase inhibitors • Sunitinib (TKI) + tumor vaccine
What do American oncologists prescribe for kidney cancer?
In conclusion, here are the interesting results of a survey with the participation of one and a half hundred leading oncologists from the United States:
• First line of therapy: doctors most often prescribe pazopanib (43%) or sunitinib (35%) • Second line of therapy: most often doctors prescribe nivolumab (63%), everolimus and cabozantinib (9% each) • Third line therapy: the leaders are cabozantinib (23%), nivolumab (22%), axitinib (17%) and everolimus (15%) • Typical duration of treatment for kidney cancer with nivolumab and cabozantinib ranges from 4 up to 8 months.
Konstantin Mokanov: Master of Pharmacy and professional medical translator
Organization of specific immunotherapy
Specific effects in renal oncology include the use of vaccines made from tumor cells. Vaccines are made from live, genetically modified tumor cells or from embryonic cells or peptides. Some types of tumor cell-based vaccines achieve good results when used simultaneously with local nephrectomy or in the absence of metastatic disease. When metastases spread, this therapy has no effect.
