Intron A is the first adjuvant therapy to surgery that has been shown to significantly increase relapse-free and overall survival in subjects with malignant melanoma. The product has previously received U.S. marketing clearance for treating hairy cell leukemia, AIDS-related Kaposi's sarcoma, condylomata acuminata, and chronic hepatitis B and C.
Intron A is an interferon, a group of naturally occurring proteins that were first discovered as a result of their ability to prevent viral replication. Additional research has determined that interferons have anti-tumor effects and are useful in fighting some types of cancer cells. Intron A is marketed in 72 countries worldwide for as many as 16 indications.
In 1985, a large, randomized, controlled phase III clinical trial conducted at 29 centers by the Eastern Cooperative Oncology Group, in conjunction with the National Cancer Institute, 280 malignant melanoma subjects were randomized to either treatment with Intron A or observation post surgery. The primary study objectives were to determine the effectiveness of Intron A in prolonging relapse-free and overall survival. A marked improvement in each of these categories was demonstrated.
In the clinical study, the addition of Intron A after surgical removal of the tumor increased median overall survival of malignant melanoma subjects by more than 12 months and median relapse-free survival by 9 months. A 24% improvement in the five-year survival rate was demonstrated. A 42% improvement in the five-year relapse-free survival rate was demonstrated for subjects receiving Intron A therapy.
Side effects included decreased white blood cell counts, fever, myalgia, anorexia, vomiting/nausea, increased liver enzyme level, headache, chills, and depression. Side effects were expected and controllable through dose modifications.
The exact mechanism of action is unknown. Intron A has been shown to have intracellular, antiviral immunomodulatory, and antiproliferative effects, in-vitro and in-vivo. These include effects on intracellular oncogene expression, stimulation of natural killer and cytotoxic T-cells, microphage activation, and induction of cytokine production. Antiproliferative effects shown include slowing of cell division and reversion of tumor cells to a normal phenotype.
Malignant melanoma is the deadliest of three main types of skin cancer; the other two are basal cell carcinoma and squamous cell carcinoma. Malignant melanoma causes approximately 7,200 deaths in the United States a year. The incidence of malignant melanoma is rising 4% each year in the United States., with 34,100 new cases expected to be diagnosed in 1995, according to the American Cancer Society.