Chawla Sant P, Chua Victoria S, Fernandez Lita, Quon Doris, Saralou Andreh, Blackwelder William C, Hall Frederick L, Gordon Erlinda M
The Sarcoma Oncology Center, Santa Monica, California, USA.
Mol Ther. 2009 Sep;17(9):1651-7. doi: 10.1038/mt.2009.126. Epub 2009 Jun 16.
Rexin-G, a pathotropic nanoparticle bearing a cytocidal cyclin G1 construct was tested in a phase I/II study for chemotherapy-resistant sarcomas and a phase II study for chemotherapy-resistant osteosarcoma. Twenty sarcoma patients and 22 osteosarcoma patients received escalating doses of Rexin-G intravenously from 8 x 10(11) to 24 x 10(11) colony forming units (cfu)/cycle. Treatment was continued if there was <or= grade 1 toxicity. No dose-limiting toxicity (DLT) was observed, and no vector DNA integration, replication-competent retrovirus (RCR) or vector-neutralizing antibodies were noted. In the phase I/II study, 3/6 patients had stable disease (SD) at the lowest dose; median progression-free survival (PFS) was 1.2 months, and overall survival (OS), 3.3 months. At higher doses, 10/14 patients had SD; median PFS was 3.7 months and median OS, 7.8 months. In this phase I/II study, a dose-response relationship with Rexin-G dosage was observed for progression-free and OS times (P = 0.02 and 0.005, respectively). In the phase II study, 10/17 evaluable patients had SD, median PFS was >or=3 months and median OS, 6.9 months. These studies suggest that Rexin-G is safe, may help control tumor growth, and may possibly improve survival in chemotherapy-resistant sarcoma and osteosarcoma.
Rexin-G是一种携带细胞毒性细胞周期蛋白G1构建体的靶向性纳米颗粒，已在一项针对化疗耐药性肉瘤的I/II期研究以及一项针对化疗耐药性骨肉瘤的II期研究中进行了测试。20例肉瘤患者和22例骨肉瘤患者静脉注射递增剂量的Rexin-G，剂量从8×10¹¹至24×10¹¹集落形成单位（cfu）/周期。如果毒性≤1级，则继续治疗。未观察到剂量限制性毒性（DLT），也未发现载体DNA整合、复制能力强的逆转录病毒（RCR）或载体中和抗体。在I/II期研究中，3/6的患者在最低剂量时病情稳定（SD）；无进展生存期（PFS）中位数为1.2个月，总生存期（OS）中位数为3.3个月。在更高剂量时，10/14的患者病情稳定；PFS中位数为3.7个月，OS中位数为7.8个月。在这项I/II期研究中，观察到无进展生存期和总生存期与Rexin-G剂量之间存在剂量反应关系（分别为P = 0.02和0.005）。在II期研究中，10/17可评估患者病情稳定，PFS中位数≥3个月，OS中位数为6.9个月。这些研究表明，Rexin-G是安全的，可能有助于控制肿瘤生长，并可能提高化疗耐药性肉瘤和骨肉瘤患者的生存率。
