Perilesional injection cutaneous melanoma of r-GM-CSF in patients with metastases

Based on evidence that granulocyte-macrophage colony stimulating factor (GM -CSF) induces a potent systemic antitumor immunity, we tested recombinant G M-CSF in advanced melanoma. Seven patients with histologically confirmed cu taneous melanoma metastases were treated with perilesional intracutaneous i njections of recombinant GM-CSF and observed for a follow-up time of 5 y. A ll but two patients had a decrease in the total number of metastases. At th e 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 di ed tumor free at the age of 93. The remaining three patients died from prog ressive melanoma. Perilesional intradermal GM-CSF therapy resulted in a mea n survival time of 33 mo. The treatment was well tolerated and no side-effe cts other than local erythema at the injection sites and mild drowsiness we re seen. Immunohistochemical analysis with staining for CD14 and GM-CSF rec eptor demonstrated an increased infiltration of monocytes into both injecte d and noninjected cutaneous melanoma metastases compared with lesions excis ed prior to the initiation of therapy. The same was true for CD4- and CD8-p ositive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyt e 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 thi s is the first report that intracutaneously injected GM-CSF results in long -lasting reduction of melanoma metastases.