Gefitinib‐induced autologous antitumor immunity

Aim:  We previously reported that thromboxane (TX) B2, p-selectin, and the cytokine that is regulated on activation, normal T expressed and secreted (RANTES) were elevated in patients with non-small cell lung cancer (NSCLC) treated with gefitinib. It is reported that macrophages are activated by platelets. We hypothesized that macrophages were activated in patients medicated with gefitinib, and we measured their plasma macrophage inflammatory protein (MIP)-1 beta. Methods:  Patients with NSCLC not curable by surgery were entered in the study and received gefitinib at a dose of 250 mg/day over a period of two weeks. Blood samples were drawn before and after administration and MIP-1 beta was measured by enzyme-linked immunosorbent assay. Results:  A total of 28 patients, 42–82-years of age (median, 67); 16 men and 12 women, were the subjects of the study: 21 had adenocarcinomas and seven squamous cancers. Partial response to gefitinib occurred in 11 patients, 12 had stable disease and five had progressive disease. The mean serum level of MIP-1 beta in the 28 evaluable patients increased significantly after gefitinib medication for 1 and 2 weeks from a baseline of 101 ± 19 pg/mL to 139 ± 25 pg/mL at one week (P < 0.05) and 131 ± 29 pg/mL at 2 weeks (P < 0.05). Conclusion:  Immunological markers related to activated platelets including MIP-1 beta as well as thromboxane A2 p-selectin and RANTES, are elevated in patients undergoing therapy with gefitinib. We speculate that gefitinib has a potential autologous immunological anti-tumor activity.