PDF(Pubmed)
Abstract：
BACKGROUND: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion.
OBJECTIVE: This study explores the efficacy of multisite intratumoral injections in improving a drug\'s distribution while minimizing its side effects.
RESULTS: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007).
CONCLUSIONS: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.
OBJECTIVE: This study explores the efficacy of multisite intratumoral injections in improving a drug\'s distribution while minimizing its side effects.
RESULTS: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007).
CONCLUSIONS: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.
摘要：
背景：局部晚期不可切除的胰腺癌（LAPC）预后不佳，肿瘤内治疗显示出有限的益处。我们假设这些肿瘤内的致密基质阻碍了药物分散。
目的：本研究探讨了多部位瘤内注射在改善药物分布同时减少其副作用方面的功效。
结果：在原位LAPC肿瘤小鼠中，与生理盐水相比,在四个不同部位每周瘤内注射奥沙利铂可使肿瘤生长减少46%(p<0.003).与吉西他滨相比，奥沙利铂对肿瘤微环境的影响最大，Abraxane,或它们的组合，随着坏死的增加，凋亡，成纤维细胞,炎症,和浸润淋巴细胞（p<0.008）。当与静脉注射FOLFIRINOX（FFX）联合使用时，与单部位注射相比,多部位瘤内奥沙利铂可使肿瘤重量减少35%(p=0.007).即使在肿瘤内治疗的10倍发生时，也没有观察到其他可见的毒性。与其他组相比，这种联合治疗显着提高了生存率（p=0.007）。
结论：多部位瘤内治疗与全身治疗相结合，有望减少LAPC的肿瘤大小和提高总体生存率。
目的：本研究探讨了多部位瘤内注射在改善药物分布同时减少其副作用方面的功效。
结果：在原位LAPC肿瘤小鼠中，与生理盐水相比,在四个不同部位每周瘤内注射奥沙利铂可使肿瘤生长减少46%(p<0.003).与吉西他滨相比，奥沙利铂对肿瘤微环境的影响最大，Abraxane,或它们的组合，随着坏死的增加，凋亡，成纤维细胞,炎症,和浸润淋巴细胞（p<0.008）。当与静脉注射FOLFIRINOX（FFX）联合使用时，与单部位注射相比,多部位瘤内奥沙利铂可使肿瘤重量减少35%(p=0.007).即使在肿瘤内治疗的10倍发生时，也没有观察到其他可见的毒性。与其他组相比，这种联合治疗显着提高了生存率（p=0.007）。
结论：多部位瘤内治疗与全身治疗相结合，有望减少LAPC的肿瘤大小和提高总体生存率。
