A new therapeutic approach in patients with advanced sarcoma

Sarcomas represent a rare and heterogeneous disease and the prognosis of patients remains poor, with a disease-free survival at 5 years of less than 10%. Only a few chemotherapeutic agents, such as doxorubicin and ifosfamide, have been identified to be active with response rates above 20%. The concept of angiostatic therapy in combination with proapoptotic biomodulators and chemotherapeutics has not been evaluated in these patients. Therefore, the efficacy of low-dose trofosfamide in combination with the peroxisome proliferator-activated receptor-gamma-agonist, pioglitazone, and the selective cyclooxygenase-2 inhibitor, rofecoxib, was evaluated in a pilot study. Six patients with advanced sarcoma received a combination of oral pioglitazone plus rofecoxib and, after 14 days, oral trofosfamide. The therapy was administered continuously daily. Four patients received the triple combination as maintenance therapy; three of them achieved stabilization of disease. Two patients received the combination as relapse therapy; however, it failed to stop disease progression. Side effects were generally mild and hospitalization was not necessary. This new triple combination of low-dose trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of sarcoma patients.