Kasper Bernd, Ho Anthony D, Egerer Gerlinde
University of Heidelberg, Department of Internal Medicine V, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Int J Clin Oncol. 2005 Dec;10(6):438-40. doi: 10.1007/s10147-005-0514-9.
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.
肉瘤是一种罕见且异质性的疾病，患者预后仍然很差，5年无病生存率低于10%。仅确定了少数几种化疗药物，如阿霉素和异环磷酰胺，具有活性，缓解率超过20%。血管生成抑制疗法与促凋亡生物调节剂和化疗药物联合使用的概念尚未在这些患者中进行评估。因此，在一项初步研究中评估了低剂量曲磷胺与过氧化物酶体增殖物激活受体γ激动剂吡格列酮和选择性环氧化酶2抑制剂罗非昔布联合使用的疗效。6例晚期肉瘤患者接受口服吡格列酮加罗非昔布联合治疗，14天后口服曲磷胺。该治疗每天持续给药。4例患者接受三联组合作为维持治疗；其中3例病情稳定。2例患者接受该组合作为复发治疗；然而，未能阻止疾病进展。副作用一般较轻，无需住院治疗。低剂量曲磷胺、吡格列酮和罗非昔布的这种新三联组合可能是肉瘤患者姑息治疗中一种可行的新选择。
