Vaccine Therapy

Unlike nonspecific immunostimulants, vaccines may be used to elicit a host immune response to known or unknown tumor antigens. A number of different melanoma vaccines have been investigated as potential adjuvants for patients with intermediate to high-risk stage IV disease. These include whole cell vaccines, shed melanoma-antigen vaccines, melanoma cell lysate vaccines, carbohydrate antigen (ganglioside-based) vaccines, and protein/peptide vaccines. Whole cell vaccines may be allogenic or autologous, and include a polyvalent allogenic vaccine comprised three irradiated allogenic melanoma cell lines (CancerVax) and AVAX, a dinitrophenyl-conjugated autologous tumor vaccine associated with the development of delayed-type hypersensitivity to melanoma cells. All of these vaccines have been preliminarily reported to have produced responses in patients with advanced disease and may have further practical use when administered in the adjuvant setting. However, few phase III trials of these vaccine preparations used alone or in combination have been conducted to date and were not associated with significant survival benefit; further trials are underway combining various vaccines with biologic agents as well.70-72 A GM2-ganglioside-based vaccine has been studied in randomized phase III trials and compared with IFN-a2b (Intergroup E1694 trial), but showed little clinical success, as elaborated earlier.15 In an effort to strengthen the responses to these (relatively) poorly immunogenic ganglio-sides, anti-idiotypic monoclonal antibody vaccines have also been developed and examined in early clinical trials. Other promising new alternatives in vaccine therapy include DNA vaccination, dendritic cell-based vaccination,

Table 51-4

Management of Primary and Metastatic Melanoma

Stage

Management

I and II (TxN0M0)

Surgical excision with appropriate margins, close follow-up possible elective lymph node dissection (ELND) or sentinel node biopsy (SNB). Reexcision and regional therapy for local recurrences

III  (TxNxM0)

IV  (TxNxMx: metastases)

Excision ELND or SNB, limb perfusion, radiotherapy, intrale sional or systemic therapy

Cutaneous, lung, gastrointestinal

Excision followed by systemic therapy

Bone

Radiotherapy

Brain

Excision, radiotherapy, systemic therapy (may need radiotherapy prior to surgery in large/multiple tumors)

Disseminated

Systemic therapy mainly; surgery and radiotherapy if symptomatic or clinically indicated


Excisional surgery is the main treatment option for all primary and most regional metastatic melanoma, followed by systemic therapy or radiotherapy as clinically indicated.


Recombinant viral vaccines, and heat-shock-protein-based vaccines.73

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