PTGS2 and melanoma: Consistently, the randomized phase II trial by Reichle et al. [22] including chemorefractory patients with progressive metastatic stage IV melanoma disease demonstrated a significantly prolonged progression-free survival if metronomic low-dose chemotherapy (trofosfamide) was combined with pioglitazone (PPARA and G agonist) and rofecoxib (COX2 inhibitor).