I. Alpha interferon
Pharmacological effects.
1, antiviral effect: its antiviral activity is not to kill but to inhibit the virus, it is generally a broad-spectrum virus inhibitor, both RNA and DNA viruses have inhibitory effects. When the recovery period of viral infection can be seen in the presence of interferon, on the other hand, with exogenous interferon can also relieve the infection.
2, inhibit cell proliferation interferon inhibit cell division activity has a significant selective, the activity of tumor cells than normal cells 500 ~ 1000 times greater. Interferon anti-tumor effect can be a direct inhibition of tumor cell proliferation, or through the host organism’s immune defense mechanism to limit the growth of tumors.
3, induction of apoptosis: interferon can induce apoptosis of tumor cells, thus killing tumor cells.
4.Interferon has immunomodulatory effects on humoral immunity and cellular immunity, and also has certain immune enhancing effects on macrophages and NK cells.
Pharmacokinetics.
Interferon is slow to enter the blood after intramuscular injection or subcutaneous injection, and takes a long time to be measured in the blood. The Tmax after intramuscular injection is 5-8 hours.
A single intramuscular injection: 106 units results in a serum concentration of 100 units/ml, which is higher than the amount of interferon naturally produced during viral infection. The half-life of interferon in the circulation is 2-4 hours. Only a small amount of interferon can enter the blood-brain barrier, and the concentration in the cerebrospinal fluid is about l/30 of the blood concentration. Excretion has been studied only in rabbits, and the excretion is only 0.2-2.0 %.
Indications.
1.Used for a variety of malignancies, including hairy cell leukemia, chronic leukemia, non-Ho lymphoma, myeloma, bladder cancer, ovarian cancer, advanced metastatic renal cancer and malignant endocrine tumors of the pancreas, melanoma and Kaposi sarcoma.
2.Used with other anti-tumor drugs.
3.As an adjuvant to radiotherapy, chemotherapy and surgery.
4.Control of viral diseases.
Usage and dosage.
Mostly administered by subcutaneous injection, intramuscular injection, intracerebrospinal cavity or intraperitoneal cavity, local instillation. The general dose of 1×106-3×106 units, subcutaneous injection or intramuscular injection, 3 times a week, can be used for several months or longer. The dose can be gradually increased or decreased according to the condition. The drug is time-dependent and maintains effective concentration for a long time with better anti-cancer effect (i.e. continuous treatment is better).
Adverse reactions.
1. Systemic reactions mainly manifest as flu-like symptoms, i.e. chills, fever and discomfort. When the dose exceeds 44×104 units/m2, fever can appear 2-6 hours after injection. With the prolongation of the treatment course, the fever can be gradually reduced, and the fever can generally stop after 7 days. To avoid fever, acetaminophen can be used beforehand. If fever still occurs, it is related to IF-α containing impurities and should not be used again.
2, bone marrow suppression in the use of drugs can appear in the white blood cells, platelets and reticulocytes reduction. Reducing the dose below 8.5×104 units/m2 can reduce the occurrence of myelosuppression.
3, local reactions some patients can appear erythema at the injection site with pressure pain, which can subside after 24 hours.
4.Other alopecia, rash, accelerated blood sedimentation, drowsiness, transient liver injury. Occasionally, anaphylaxis is seen, and allergy test is performed before the drug is administered.
Interactions.
Prednisone or other corticosteroids have the effect of reducing the biological activity of interferon and should be noted.
Precautions.
1, Myocardial infarction, severe hypertension, cerebrovascular disease use with caution.
2.If lyophilized preparation is found to be shrunken, discolored, liquid preparation is cloudy, there are foreign bodies or insoluble precipitation, etc. should not be used.
3.It is not suitable for oral and static injection.
4.Store at 1-4℃.
Efficacy evaluation.
1.Significant efficacy for a variety of malignant tumors Interferon for hairy cell leukemia efficiency up to 80%; for chronic leukemia CR up to 69%, IF-α instrument therapy has become a standard treatment for chronic granulocytic leukemia; for non-he lymphoma efficiency of 65%; for myeloma 15%-25%; for acute leukemia only moderate efficacy; for bladder cancer, ovarian cancer, advanced metastatic It is also effective against bladder cancer, ovarian cancer, advanced metastatic kidney cancer and pancreatic malignant endocrine tumor; 15%-25% for melanoma IF-α; 35%-50% for Kaposi’s sarcoma of AIDS.
2.It can significantly improve the efficacy when used with other antitumor drugs; it has better efficacy when used with DTIC to treat disseminated malignant melanoma; it has synergistic effect when used with ADM to treat ovarian cancer and pancreatic cancer, etc. The overall response rate of 5-fluorouracil combined with interferon for advanced gastrointestinal cancer, especially colon cancer and esophageal cancer, is up to 63%.
3.In clinical application, it is mostly used as an adjuvant to radiotherapy, chemotherapy and surgery. For example, it can reduce radiation reaction and improve immune function of patients when used with radiotherapy for bladder cancer.
4.It is effective in the prevention and treatment of viral diseases, such as warts caused by papilloma virus, keratitis caused by herpes simplex virus, cold caused by rhinovirus and herpes zoster. It has certain effect on hepatitis B.