Abstract
Advanced Stage IV and IIIc melanoma has a dismal survival, with or without, standard chemotherapy. New therapies are required to improve survival and reduce morbidity. Repeated vaccine dosing does not appear to have been explored, so Vaccinia Melanoma Cell Lysate (VMCL) vaccine repetitive therapy was tested, either alone, or combined with chemotherapy. 37 patients (31 Stage IV [M1a(6), b(7), c(18)] and 6 Stage IIIc) were studied using intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was assessed and clinical responses were also recorded. From vaccine commencement, median overall follow-up was 10 months. Survivals ranged from 4 to 73 months. Median (mean) overall survival was 10 (23.5) months; overall survival at 1, 2 and 3 years was 40.5%, 21.6% and 10.8% respectively. CR and PR occurred in 18.9% (7) and 18.9% (7) of patients; these were durable for up to 6.1 years in 4 patients. Stable disease was noted in a further 17 patients (45.9%). In 6 patients (16.2%) no response to therapy was apparent. Repeated vaccinations with or without chemotherapy produced strong, durable clinical responses with overall survival > 23 months occurring in nearly 25% of advanced melanoma patients. The overall disease control rate (CR, PR and SD) was 83.7%, including CR in very advanced cases. These results, in a largely unselected population of advanced metastatic melanoma patients, compare very favourably with other regimens, and notably were associated with minimal, if any, toxicity. Further analysis of this approach appears warranted.
Highlights
Current therapies for advanced disseminated melanoma or locally advanced disease remain seriously inadequate with typically poor clinical responses, high failure rates even when responses do occur, and options for any subsequent therapy are severely limited
Immunotherapy using vaccines has been used previously, but most studies have not persisted with continued vaccinations when disease progression has occurred, and especially when chemotherapy is administered, typically using either Dacarbazine (DTIC) or Fotemustine, which are considered as the standard treatment agents
A possible innovative role for combined continued immuno-chemotherapy is suggested by these results in the treatment of advanced non-resectable melanoma that has failed surgery and/or other therapies
Summary
Current therapies for advanced disseminated melanoma or locally advanced disease remain seriously inadequate with typically poor clinical responses, high failure rates even when responses do occur, and options for any subsequent therapy are severely limited. Immunotherapy using vaccines has been used previously, but most studies have not persisted with continued vaccinations when disease progression has occurred, and especially when chemotherapy is administered, typically using either Dacarbazine (DTIC) or Fotemustine, which are considered as the standard treatment agents. These standard chemotherapy agents are often regarded as essentially palliative for ameliorating symptoms from metastases, but to our knowledge have seldom been tested with concurrent vaccine or other immunotherapies, apart from the interferons. Immunotherapy with dendritic cell vaccines has been effective in a number of small studies, but results have
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