Interferon-alpha (IFN-α) and interleukin-2 (IL-2) have been used to treat advanced kidney cancer since the 1990s. Although overall, these cytokine treatments are less effective than targeted drugs, they are still effective in most patients with metastatic clear cell carcinoma. Together with relatively low toxic side effects, relatively inexpensive and reimbursable by health insurance, interferon-alpha and interleukin-2 are still recommended for the treatment of advanced kidney cancer in China.
Interferon-alpha (IFN-α)
IFN-α is a natural glycoprotein produced by the body in response to viral infections and foreign antigens, and is the first genomic cytokine to be used clinically.
Clinical studies have demonstrated that medium- and high-dose IFN-α (9 million units or more) treatment of patients with metastatic kidney cancer more than doubles progression-free survival (PFS) compared with placebo. The clinical outcome was particularly good in those patients with low- to intermediate-risk renal clear cell carcinoma.
But IFN-α alone has limited efficacy in treating advanced kidney cancer. Foreign studies have found that bevacizumab combined with IFN-α has better remission rates and progression-free survival than IFN-α alone. As a result, authoritative guidelines such as the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU) have recommended bevacizumab in combination with IFN-α as a first-line treatment option for metastatic kidney cancer.
Interleukin-2 (IL-2)
IL-2 is a lymphocytokine produced primarily by mature T lymphocytes and is dependent on the growth and maturation of T cells and natural killer cells (NK cells). Its biological properties and clinical applications have been extensively studied over the past 20 years.
The major functions of IL-2 in the immune system include:
- IL-2 binds to membrane surface receptors and activates T lymphocytes and monocytes, resulting in clonal expansion of antigen-specific T cells and enhanced immune response.
- Stimulates monocytes to express other cytokines such as IFN, tumor necrosis factor (TNF) and promotes secretion of other cytokines.
- Enhance the anti-tumor effect of NK cells, LAK cells (lymphokine-activated killer cells) and other killer cells.
According to a clinical study of 255 patients with metastatic renal cell carcinoma treated with high-dose IL-2, the overall treatment response rate was 15%, with a complete remission (complete disappearance of tumor) rate of 7% and a partial remission (tumor shrinkage of 30% compared to pre-treatment) rate of 8%.
It is worth noting that most of these patients who achieved complete remission survived long term, which is equivalent to a cure! It can be said that IL-2 is a milestone in the history of advanced kidney cancer because all previous treatments, including chemotherapy, radiation, hormone therapy, etc., have not achieved such good results. The FDA approved “high-dose IL-2” as a first-line treatment for advanced kidney cancer because of its clear efficacy in kidney cancer.
However, in order to achieve such efficacy, patients must be brave enough to receive high doses of IL-2, 600,000 to 720,000 units of IL-2 per kilogram of body weight given intravenously every 8 hours, for a total of 14 injections, and the treatment needs to be repeated after a 10-day break. This is very physically taxing and is usually only tolerated by patients in very good health.
Side effects and management measures
The severity of cytokine toxicities varies depending on the mode of administration, dose, and treatment regimen. The side effects of low doses of IL-2 or IFN-α usually resolve on their own when the drug is discontinued or treatment ends.
Common clinical side effects of cytokine therapy include:
- Flu-like symptoms: high fever, chills, headache, muscle aches and pains, which may be treated with anti-inflammatory pain or paracetamol as adjunctive therapy or prophylaxis during the course of treatment.
- Gastrointestinal symptoms: nausea and vomiting, which can be treated with antiemetic medications.
- Capillary leak syndrome: This is the most serious and frightening side effect of high-dose IL-2, mainly due to increased vascular permeability, causing transfer of body fluids from intravascular to intertissue, resulting in decreased circulating blood volume, hypotension, tachycardia, oliguria, ascites, pulmonary edema, and should be promptly supplemented with crystalloid fluid, but limited to & nbsp;1~2 liters, and if necessary, apply alpha-adrenergic agonists, such as phenylephrine to raise blood pressure as well as dopamine to improve renal blood perfusion and prevent the occurrence of renal insufficiency.
- Infection: The incidence is 10% to 30%, and antibiotics can be used to prevent the occurrence of infection.
Very few patients experience lethal adverse effects, such as myocardial infarction, arrhythmias, and respiratory failure, so patients must be rigorously evaluated for cardiopulmonary function before treatment, and high-dose IL-2 or IFN-α therapy should not be given if cardiopulmonary function is poor, for the sake of patient personal safety.