Boyé Pierre, Floch Franck, Serres François, Segaoula Zacharie, Hordeaux Juliette, Pascal Quentin, Coste Virginie, Courapied Sandy, Bouchaert Emmanuel, Rybicka Agata, Mazuy Claire, Marescaux Laurent, Geeraert Kévyn, Fournel-Fleury Corinne, Duhamel Alain, Machuron François, Ferré Pierre, Pétain Aurélie, Guilbaud Nicolas, Tierny Dominique, Gomes Bruno
OCR (Oncovet-Clinical-Research), Loos, France.
Oncovet, Villeneuve d'Ascq, France.
Oncotarget. 2020 Feb 18;11(7):671-686. doi: 10.18632/oncotarget.27461.
F14512 is an epipodophyllotoxin derivative from etoposide, combined with a spermine moiety introduced as a cell delivery vector. The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma (NHL) and to investigate the potential benefit of F14512 in P-glycoprotein (Pgp) overexpressing lymphomas. Forty-eight client-owned dogs with intermediate to high-grade NHL were enrolled into a randomized, double-blind trial of F14512 etoposide phosphate. Endpoints included safety and therapeutic efficacy. Twenty-five dogs were randomized to receive F14512 and 23 dogs to receive etoposide phosphate. All adverse events (AEs) were reversible, and no treatment-related death was reported. Hematologic AEs were more severe with F14512 and gastrointestinal AEs were more frequent with etoposide phosphate. F14512 exhibited similar response rate and progression-free survival (PFS) as etoposide phosphate in the global treated population. Subgroup analysis of dogs with Pgp-overexpressing NHL showed a significant improvement in PFS in dogs treated with F14512 compared with etoposide phosphate. F14512 showed strong therapeutic efficacy against spontaneous NHL and exhibited a clinical benefice in Pgp-overexpressing lymphoma superior to etoposide phosphate. The results clearly justify the evaluation of F14512 in human clinical trials.
F14512是依托泊苷的一种表鬼臼毒素衍生物，并结合了作为细胞递送载体引入的精胺部分。本研究的目的是比较F14512和磷酸依托泊苷在患有自发性非霍奇金淋巴瘤（NHL）的犬中的安全性和抗肿瘤活性，并研究F14512在过表达P-糖蛋白（Pgp）的淋巴瘤中的潜在益处。48只患有中高级NHL的客户拥有的犬被纳入F14512与磷酸依托泊苷的随机双盲试验。终点包括安全性和治疗效果。25只犬被随机分配接受F14512，23只犬接受磷酸依托泊苷。所有不良事件（AE）均为可逆性，且未报告与治疗相关的死亡。F14512导致的血液学AE更严重，而磷酸依托泊苷导致的胃肠道AE更频繁。在全球治疗人群中，F14512表现出与磷酸依托泊苷相似的缓解率和无进展生存期（PFS）。对过表达Pgp的NHL犬的亚组分析显示，与磷酸依托泊苷相比，接受F14512治疗的犬的PFS有显著改善。F14512对自发性NHL显示出强大的治疗效果，并且在过表达Pgp的淋巴瘤中表现出优于磷酸依托泊苷的临床益处。这些结果明确证明了在人类临床试验中对F14512进行评估的合理性。
