Interferon-alfa2b Treatment for Melanoma

Treatment for Melanoma Skin Cancer is Lengthy and Challenging

The standard initial treatment for melanoma is the surgical removal of any lesions, a procedure called wide area excision. Depending on the stage of your tumor, your healthcare provider may then recommend an adjuvant (after surgery) treatment to lessen the chance that the melanoma will come back (recur). For example, if the melanoma has spread to one or more of your lymph nodes, there is an estimated 70% to 80% chance that the melanoma will recur within the next three to five years. FDA-approved adjuvant treatment options include ipilimumab, nivolumab, dabrafenib + trametinib, pembrolizumab, and interferon. If your oncologist has recommended interferon-alfa2b, this overview will arm you with the critical information you need to understand how it works, its effectiveness and its side effects.

Dermatologist examines a mole
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Also called interferon-alpha2b, IFN and Intron A, Interferon-alfa2b was approved by the Food and Drug Administration (FDA) in 1995. The drug is approved for use within 56 days (8 weeks) after surgery in patients 18 years of age or older with malignant melanoma who are free of the disease but are at a high risk for recurrence (the tumor coming back). Patients at a high risk for recurrence include those with melanoma in the following stages:

  • Stage IIB: tumors more than 4 mm (about 1/6 of an inch) thick with no ulceration or 2 mm to 4 mm with ulceration
  • Stage IIC: tumors more than 4 mm thick with ulceration
  • Stage IIIA, IIIB, IIIC: tumors can be any size but the disease has spread to the lymph nodes

Interferon-alfa2b is different than a chemotherapy drug; it is actually a natural part of your body's immune system. It is known as a cytokine, which are chemicals normally secreted by cells called leukocytes in response to a virus, bacteria, or other foreign intruders. It then attaches to other cells and causes a complex series of changes (many of which are unknown), including slowing down the rate of cell division and reducing cells' ability to protect themselves from the immune system.

IFN used to treat melanoma doesn't come from the body but rather is mass-produced in a laboratory using the techniques of genetic engineering. It has the same properties as the natural version but technically is called "recombinant" for this reason.

Evidence for the Effectiveness of Interferon-alfa2b

IFN is the only medication for people with high-risk malignant melanoma that has been shown to improve both relapse-free survival (living without the disease coming back) and overall survival. Three studies led to its approval by the FDA. First, high-dose IFN was compared to doing nothing: In this case, those treated with IFN didn't relapse as quickly and lived a year longer on average. In the second trial, high-dose IFN was compared to low-dose IFN and again there was a significant increase in relapse-free survival in the high-dose group. However, there was no difference in overall survival. Finally, when IFN was compared to an experimental vaccine called GMK, the results were clear: the IFN group had a 47 percent improvement in relapse-free survival and a 52 percent improvement in overall survival.

Many other clinical trials have been conducted (and are still being conducted) in an attempt to increase the effectiveness of IFN. Unfortunately, some later studies didn't show as large a positive effect as the original ones, and one 2008 study (called the "Sunbelt" trial) showed no effect of IFN on patients with one positive sentinel lymph node, so the use of IFN has been controversial among healthcare providers. Indeed, oncologists in Europe have been especially reluctant to prescribe IFN due to perceptions about its small benefit and significant toxicity. If you have any questions or concerns, be sure to discuss them with your healthcare provider.

Use of Interferon-alfa2b

After surgery, IFN is given in two steps: induction and maintenance. Induction involves receiving a high dose at a hospital with an IV (intravenous) infusion over 20 minutes, five consecutive days per week, for four weeks. During the maintenance phase, you inject a lower dose of IFN yourself at home three times per week for 48 weeks. It is injected just under the skin (subcutaneously), usually in the thigh or abdomen. You or a relative will be taught how to give these injections by the nurse or healthcare provider.

Potential Side Effects of Interferon-alfa2b

Treatment with IFN is lengthy and challenging. However, with appropriate monitoring, dose modifications, and aggressive supportive care, it can be given safely and is manageable for the majority of patients. The two most common side effects of IFN are flu-like symptoms (fever, chills, muscle and joint aches) and fatigue. To help ease these symptoms, follow the "ABCs":

  • Acetaminophen (Tylenol)
  • Bedtime administration (do the injections before going to bed)
  • Conserve energy
  • Drink plenty of fluids
  • Eat balanced meals
  • Focus on the positive

The flu-like symptoms usually decrease over the course of the treatment but the fatigue usually persists and may even get worse.

The following side effects are less frequent but have been reported in many people taking IFN:

  • Nausea, vomiting
  • Fever
  • Fatigue
  • Skin irritation at the injection site
  • Dizziness
  • Depression, suicidal thoughts, and other emotional problems
  • "Pins and needles" feeling in hands and feet
  • Hair loss
  • Decreased white blood cell production, which can lead to more infections and anemia
  • Changes in liver function
  • Changes in heart rhythm and blood pressure

Other side effects are possible so be sure to discuss them with your healthcare provider. Most side effects will go away once interferon-alfa2b therapy is stopped.


IFN may worsen some of your pre-existing conditions, so tell your healthcare provider if you have:

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By Timothy DiChiara, PhD
Timothy J. DiChiara, PhD, is a former research scientist and published writer specializing in oncology.