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.
Kasper
Bernd
B
University of Heidelberg, Department of Internal Medicine V, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. Bernd.Kasper@med.uni-heidelberg.de
Ho
Anthony D
AD
Egerer
Gerlinde
G
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010166:Palliative Care; D010865:Pilot Projects; D000077205:Pioglitazone; D012509:Sarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D013450:Sulfones / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D007783:Lactones; D013450:Sulfones; D045162:Thiazolidinediones; C116926:rofecoxib; D003520:Cyclophosphamide; C003726:trofosfamide; D000077205:Pioglitazone