Cumashi Albana, Tinari Nicola, Rossi Cosmo, Lattanzio Rossano, Natoli Clara, Piantelli Mauro, Iacobelli Stefano
Department of Oncology and Neurosciences, "G. D'Annunzio" University and Foundation Chieti-Pescara, Via dei Vestini 5, Chieti 66013, Italy.
Cancer Lett. 2008 Nov 8;270(2):229-33. doi: 10.1016/j.canlet.2008.05.007. Epub 2008 Jun 30.
The aim of the study was to evaluate the activity of the antiangiogenic agent SU-11248 (sunitinib malate, Sutent), alone or in combination with docetaxel. To this end, animals bearing DU-145 human hormone-refractory prostate cancer (HRPC) xenografts were treated with sunitinib (40 mg/kg daily, p.o.), docetaxel (10 or 30 mg/kg/week, i.v.), a combination of sunitinib (40 mg/kg daily) and docetaxel (10 mg/kg/week) or vehicle alone. At the end of the 3-week dosing schedule, single-agent treatment induced a tumor regression of 59%, 49% and 75% for sunitinib, docetaxel 10mg/kg, and docetaxel 30 mg/kg, respectively. The combination of sunitinib with low-dose (10mg/kg) docetaxel produced a tumor regression comparable to that obtained with high-dose (30 mg/kg) docetaxel, but tolerability was higher as indicated by mice weight. Both sunitinib and docetaxel inhibited tumor regrowth after initial treatment with the alternate drug. These results suggest that sunitinib alone or in combination with low-dose docetaxel may have a role in the treatment of HRPC.
本研究的目的是评估抗血管生成药物SU-11248(苹果酸舒尼替尼,索坦)单独使用或与多西他赛联合使用的活性。为此,对携带DU-145人激素难治性前列腺癌(HRPC)异种移植瘤的动物进行了以下治疗:舒尼替尼(每日40mg/kg,口服)、多西他赛(每周10或30mg/kg,静脉注射)、舒尼替尼(每日40mg/kg)与多西他赛(每周10mg/kg)联合使用或仅使用赋形剂。在3周给药方案结束时,单药治疗使舒尼替尼、10mg/kg多西他赛和30mg/kg多西他赛的肿瘤消退率分别为59%、49%和75%。舒尼替尼与低剂量(10mg/kg)多西他赛联合使用产生的肿瘤消退与高剂量(30mg/kg)多西他赛相当,但小鼠体重表明耐受性更高。舒尼替尼和多西他赛在先用另一种药物进行初始治疗后均抑制了肿瘤再生长。这些结果表明,舒尼替尼单独使用或与低剂量多西他赛联合使用可能在HRPC的治疗中发挥作用。