Based on evidence that
granulocyte-macrophage colony stimulating factor (
GM-CSF) induces a potent systemic antitumor immunity, we tested recombinant
GM-CSF in advanced
melanoma. Seven patients with histologically confirmed cutaneous
melanoma metastases were treated with perilesional intracutaneous
injections of recombinant
GM-CSF and observed for a follow-up time of 5 y. All but two patients had a decrease in the total number of
metastases. At the end of the 5 y follow-up three of the seven patients are still alive with only one patient receiving other than surgical
therapy, and one patient died
tumor free at the age of 93. The remaining three patients died from progressive
melanoma. Perilesional intradermal
GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well tolerated and no side-effects other than local
erythema at the injection sites and mild drowsiness were seen. Immunohistochemical analysis with staining for CD14 and
GM-CSF receptor demonstrated an increased infiltration of monocytes into both injected and noninjected cutaneous
melanoma metastases compared with lesions excised prior to the initiation of
therapy. The same was true for CD4- and CD8-positive lymphocytes. This phenomenon, together with
GM-CSF-induced leukocyte counts of more than 20,000 during
therapy, support the possible impact of a systemic over a locally induced reaction by
GM-CSF. To our knowledge this is the first report that intracutaneously injected
GM-CSF results in long-lasting reduction of
melanoma metastases.