Melanoma adjuvant therapy

Interferon-a2b is approved by the Food and Drug Administration (FDA) as adjuvant therapy for high-risk melanoma. 

Kefford RF. Adjuvant therapy of cutaneous melanoma The interferon debate. Ann Oncol 2003 14 358-365. 

Spitler, L.E. et al., Adjuvant therapy of stage HI and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor, J Clin Oncol, 18, 1614, 2000. 

G. Other applications Leukine has been effective in producing increases in normally functioning neutrophils, eosinophils, and monocytes in AIDS patients and patients with leukopenia. Leukine may prolong survival when used as adjuvant therapy in patients with stage III or IV malignant melanoma. Leukine has also been effective in abrogating chemotherapy-related neutropenia in cancer patients, with a reduction in the severity and duration of chemotherapy-induced myelosuppression. 

Lawson DH Choices in adjuvant therapy of melanoma. Cancer Control 2005 12 236. [PMID 16258495]... 

Haluska FG. Adjuvant therapy of melanoma with inter-feron-alpha-2b is associated with mania and bipolar syndromes. Cancer 2000 89(2) 356-62. 

Greenberg DB, Jonasch E, Gadd MA, Ryan BF, Everett JR, Sober AJ, Mihm MA, Tanabe KK, Ott M, Haluska FG. Adjuvant therapy of melanoma with inter-feron-alpha-2b is associated with mania and bipolar syndromes. Cancer 2000 89(2) 356-62. 

Gutman H, Schachter J, Stopel E, Gutman R, Lahav J. Impaired platelet aggregation in melanoma patients treated with interferon-alpha-2b adjuvant therapy. Cancer 2002 94(3) 780-5. 

In addition to these uses, IL-2 has been found to be effective in the treatment of patients with disseminate cancer of the kidney and melanoma and in adjuvant therapy of acute myeloid leukemia. Attempts have been made to apply it in the treatment of AIDS and leprosy. The most common areas for IL-2 therapy are renal ceU carcinoma, melanoma, and lymphoma. ... 

The risk of relapse and death after the resection of a local or regional cutaneous melanoma is the primary determinant for the use of adjuvant therapy after primary resection. Adjuvant trials have focused on patients at intermediate or high risk of recurrence. 

Because of the associated toxicity and adverse effects seen with interferon-a therapy there has been worldwide concern about the usefulness of this intensive adjuvant therapy for melanoma despite the possible benefits in relapse-free and overall survival. A subsequent report from the cooperative group study demonstrated a quality-of-life benefit with interferon therapy based on the quality-of-life-adjusted survival analysis. This analysis calculates the quality-of-life-adjusted years gained as a result of interferon-a treatment or the clinical benefit of time without toxicities and without disease. 

There is significant controversy regarding the role of interferon-a as adjuvant therapy in high-risk patients after surgical resection of melanoma. Assessment of patient risk factors, availability of clinical trials, and cost of therapy should be evaluated prior to initiation of therapy. 

The role of interferon in advanced disease is even more unclear, especially for those patients who have recurred after treatment with adjuvant interferon therapy. Interferon-a has been used as a single agent in patients with metastatic disease who have not received adjuvant therapy, and in combination with chemotherapy and/or other biotherapy for metastatic melanoma. The challenges of combination therapy are that many of the toxicities seen with interferon can be exacerbated by concomitant chemotherapy (e.g., nausea, vomiting, and neutropenia). In an attempt to limit systemic toxicity and to potentate local benefits, the regional administration has been evaluated in a variety of settings. Intralesional and perilesional application of interferon has been shown to have some efficacy in small lesions and appears to be well tolerated. ... 

Kirkwood JM, Straderman MH, Ernstoff MS, et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutanteous melanoma The Eastern cooperative oncology group trial EST 1684. J Clin Oncol 1996 14 7-17. 

Moschos SJ, Kirkwood JM. Present status and future prospects for adjuvant therapy of melanoma Time to build upon the foundation of high-dose interferon alfa-2b. J Clin Oncol 2004 22 11-14. 

Based on these studies, IFN-a was introduced as standard adjuvant therapy for stage III resected melanoma. However, toxicity remains an issue. Flu-like syndromes including fever, chills, headache, malaise, myalgias, arthralgias, and fatigue acutely occur during therapy with interferons and diminish over time with continued daily or alternate daily administration. Vigorous hydration is essential, as patients tend to become dehydrated. 

Grob JJ, Dreno B, de la SP, Delaunay M, Cupissol D, GuiJlot B et al (1998) Randomized trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metas-tases. French Cooperative Group on Melanoma. Lancet 351 1905-1910... 

Several clinical trials of isotretinoin have been initiated. Ongoing studies in advanced cancers include chronic myelogenous leukemia, carcinoma of the head and neck, and myelodysplastic syndromes. Adjuvant therapy trials are ongoing in non-small cell lung cancer, head and neck carcinoma, and malignant melanoma. Most of these trials utilize a randomized double-blind design. Unfortunately, for most of these studies (especially the adjuvant trials) definitive results will not be available for several years. 

Skin A patient developed two histologically confirmed subcutaneous sarcoid nodules 15 months after starting adjuvant therapy with interferon for lymph node metastatic melanoma in which the primary tumor was not known [52" ]. As imaging techniques do... 

Most patients with thin local (stage I) melanoma can be cured by local excision and do not require adjuvant therapy. However, melanoma is an extremely aggressive disease with high metastatic potential and a notoriously high resistance to cytotoxic agents. There are several approved postoperative adjuvant therapies for malignant melanoma. Interferon-a (IFN-a) is the most commonly used adjuvant immunotherapy for advanced melanoma. High-dose interleukin-2 (IL-2) has... 

Johnson DM, Hayat SQ, Burton GV. Rheumatoid arthritis complicating adjuvant interferon-alpha therapy for malignant melanoma. J Rheumatol 1999 26(4) 1009-10. 

An effective treatment for the deadly skin cmicer melanoma is clearly needed. Current best therapy is surgical removal of high-risk melanoma and treatment with Interferon alfa. Melanoma patients have a 50-80% chance of relapse without adjuvant treatment. The (jMK vaccine is in development for melanoma... 

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