Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

Inclusion Criteria:

* Patients must be considered a candidate for adjuvant IFN-alpha-2b therapy after having undergone successful surgery for high-risk melanoma (Breslow thickness \> 4 mm or lymph node disease) or complete resection of metastatic disease; definitive surgery should have been accomplished no greater than 90 days prior to start of treatment with intravenous IFN-alpha-2b
* Patients must have completed 20 treatments of intravenous IFN-alpha-2b according to standard practice within 2 months of beginning treatment on this study
* Patients must have not have any evidence of persistent or recurrent disease as determined by the appropriate radiologic imaging techniques
* Patients may have received prior IFN-alpha therapy for metastatic disease, but more than 6 months must have passed between the last dose of IFN-alpha therapy for metastatic disease and the first dose of intravenous IFN-alpha-2b; patients who have had prior interleukin (IL)-2 are eligible for this study
* Patients may have received radiation therapy after intravenous IFN-alpha-2b; they may begin subcutaneous dosing of IFN-alpha-2b on this study after the radiation therapy has been completed; the patient may initiate dose reductions after the last radiation treatment as long as the appropriate amount of time has passed
* Life expectancy of greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 70%)
* Leukocytes \>= 3,000/ul
* Absolute neutrophil count \>= 1,500/ul
* Platelets \>= 100,000/ul
* Total bilirubin =\< 2.0 (Gilbert's disease permitted)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) \< 3 x institutional upper limit of normal
* Creatinine =\< 1.5 and stable OR
* Creatinine clearance \>= 60 mL.min/1.73 m\^2 for patients with creatinine levels above normal
* Pulse oximetry \>= 90% on room air at rest
* Serum pregnancy test negative
* The effects of interferon alpha-2b on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, and because interferons are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* All patients must be informed of the investigational nature of this study and must provide written informed consent in accordance with institutional and federal guidelines; a copy of the informed consent document signed by the patient must be given to the patient

Exclusion Criteria:

* Patients may not be receiving any investigational agents
* History of allergic reactions attributed to compounds that are similar to interferon alpha-2b
* Patients known to be positive for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbsAg) or hepatitis C antibody
* Patients with organ allografts or immunodeficiency syndromes
* Patients with prior malignancies may participate provided they have been free of disease for at least 2 years except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; a history of depression in and of itself is not an exclusion to going participating provided the patient and physician believe the depression is controlled and the patient will discontinue the IFN-alpha should symptoms recur
* Pregnant women are excluded from this study because interferon alpha-2b is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IFN-alpha, breastfeeding should be discontinued if the mother is treated with IFN-alpha
* Prisoners will be excluded due to the need for multiple timed visits