Ahluwalia Manmeet S, Chao Samuel T, Parsons Michael W, Suh John H, Wang Ding, Mikkelsen Tom, Brewer Cathy J, Smolenski Kathy N, Schilero Cathy, Rump Matthew, Elson Paul, Angelov Lilyana, Barnett Gene H, Vogelbaum Michael A, Weil Robert J, Peereboom David M
Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
J Neurooncol. 2015 Sep;124(3):485-91. doi: 10.1007/s11060-015-1862-6. Epub 2015 Aug 6.
Patients with 1-3 brain metastases (BM) often receive sterotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT). SRS without WBRT carries a high rate of relapse in the central nervous system (CNS). This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Eligible patients with 1-3 newly diagnosed BM, RTOG RPA class 1-2, received sunitinib after SRS. Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/days 1-28 every 42 days until CNS progression. Neuropsychological testing and MRIs were obtained every two cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Fourteen patients with a median age of 59 years were enrolled. Primary cancers included lung 43 %, breast 21 %, melanoma 14 %. Toxicity included grade 3 or higher fatigue in five patients and neutropenia in two patients. The CNS PFS6 and PFS12 were 43 ± 14 and 34 ± 14 %, respectively. Of the ten patients who completed >1 neurocognitive assessment, none showed cognitive decline. Sunitinib after SRS for 1-3 BM was well tolerated with a PFS6 of 43 %. The prevention of progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient's primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of BM after definitive local therapy.
患有1 - 3个脑转移瘤（BM）的患者通常接受立体定向放射外科治疗（SRS）而不进行全脑放疗（WBRT）。不进行WBRT的SRS会导致中枢神经系统（CNS）的高复发率。本试验使用舒尼替尼替代WBRT进行SRS后的辅助治疗。符合条件的1 - 3个新诊断BM、RTOG RPA 1 - 2级的患者在SRS后接受舒尼替尼治疗。全身疾病得到控制的患者可根据方案中列出的已发表方案清单（化疗 + 舒尼替尼）继续对其原发性疾病进行化疗。患者每42天服用舒尼替尼37.5或50mg/天，共28天，直至CNS进展。每两个周期进行神经心理学测试和MRI检查。主要终点是SRS后6个月时的CNS进展率（PFS6）。纳入了14名中位年龄为59岁的患者。原发性癌症包括肺癌43%、乳腺癌21%、黑色素瘤14%。毒性反应包括5名患者出现3级或更高等级的疲劳，2名患者出现中性粒细胞减少。CNS的PFS6和PFS12分别为43±14%和34±14%。在完成>1次神经认知评估的10名患者中，无人出现认知能力下降。SRS后使用舒尼替尼治疗1 - 3个BM耐受性良好，PFS6为43%。SRS后预防进行性脑转移需要纳入化疗方案以控制患者的原发性疾病。未来的试验应继续探索确定性局部治疗后BM的二级化学预防模式。
