Vogt Thomas, Hafner Christian, Bross Klaus, Bataille Frauke, Jauch Karl-Walter, Berand Anna, Landthaler Michael, Andreesen Reinhard, Reichle Albrecht
Department of Dermatology, University of Regensburg, Regensburg, Germany.
Cancer. 2003 Nov 15;98(10):2251-6. doi: 10.1002/cncr.11775.
Systemic therapy options for patients with advanced angiosarcomas are limited, and their prognosis is poor. The idea of angiostatic therapy following the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic biomodulators had not been considered previously in these patients. Therefore, in a pilot study, the efficacy of metronomically scheduled, low-dose trofosfamide in combination with the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, and the selective cyclooxygenase-2 inhibitor, rofecoxib, was evaluated in patients with advanced vascular malignancies.
Six patients with advanced and pretreated but progressive, malignant vascular tumors (5 angiosarcomas and 1 hemangioendothelioma) received a combination of pioglitazone (45 mg per day orally) plus rofecoxib (25 mg per day orally) and, after 14 days, trofosfamide (3 x 50 mg per day orally). The therapy was administered continuously until progression was observed. If necessary, doses were modified according to side effects.
Two patients responded with complete remission of disease, one patient responded with partial remission, and three patients achieved stabilization of disease (no change). The median progression-free survival was 7.7 months (range, 2-15 months). Side effects generally were mild (World Health Organization Grade 1-2). Hospitalization was not necessary.
This new triple combination of low-dose metronomic trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of patients with advanced malignant vascular tumors.
晚期血管肉瘤患者的全身治疗选择有限，预后较差。此前，这些患者尚未考虑过按照节拍给药化疗药物与促凋亡生物调节剂相结合的血管生成抑制疗法。因此，在一项试点研究中，对晚期血管恶性肿瘤患者评估了节拍给药的低剂量曲磷胺联合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抑制剂罗非昔布的疗效。
6例晚期且经过预处理但病情仍进展的恶性血管肿瘤患者（5例血管肉瘤和1例血管内皮瘤）接受吡格列酮（每日口服45 mg）加罗非昔布（每日口服25 mg）联合治疗，14天后加用曲磷胺（每日口服3次，每次50 mg）。持续给药直至观察到病情进展。必要时，根据副作用调整剂量。
2例患者疾病完全缓解，1例患者部分缓解，3例患者病情稳定（无变化）。无进展生存期的中位数为7.7个月（范围为2 - 15个月）。副作用一般较轻（世界卫生组织1 - 2级）。无需住院治疗。
低剂量节拍给药的曲磷胺、吡格列酮和罗非昔布的这种新三联组合可能是晚期恶性血管肿瘤患者姑息治疗中一种可行的新选择。
