Rohde D, Goertz M, Blatter J, Jakse G
Department of Urology, University of Aachen, D-52057 Aachen, Germany.
Int J Oncol. 1998 Jun;12(6):1367-72. doi: 10.3892/ijo.12.6.1367.
Recent in vitro experiments indicated strong activity of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) in human renal cell carcinoma (RCC) cell lines and an increase of efficacy by combined application of interferon (IFN). In the present study, nude mice with xenografts from ACHN- or SN12C cells were treated by dFdC, dFdC plus IFN-alpha or vinblastine (VBL) plus IFN-alpha. ACHN-xenografts were significantly more inhibited by dFdC+/-IFN-alpha than by VBL+IFN-alpha. Complete remissions (CR) were only seen by dFdC. An additional treatment with IFN-alpha shortened the time to commencement of tumor remission and increased CR of ACHN- and SN12C-tumors (40%; 7%) compared to a treatment with dFdC alone (20%; 0). dFdC+IFN-alpha reduced the number of pulmonary metastases compared to untreated animals. Survival was significantly prolonged by dFdC+/-IFN-alpha in ACHN-mice and dFdC+IFN-alpha or VBL+IFN-alpha in SN12C mice. In conclusion, experimental data confirm dFdC as a superior drug against human RCC compared to VBL. Combined therapy with IFN-alpha increased the efficacy of dFdC in terms of tumor response in immunodeficient nude mice, thus clinical studies are strongly recommended in patients with metastatic renal cell carcinoma.
近期的体外实验表明，2',2'-二氟脱氧胞苷（dFdC，吉西他滨）在人肾细胞癌（RCC）细胞系中具有很强的活性，并且联合应用干扰素（IFN）可提高疗效。在本研究中，将接种了ACHN或SN12C细胞异种移植物的裸鼠分别用dFdC、dFdC加IFN-α或长春碱（VBL）加IFN-α进行治疗。与VBL加IFN-α相比，dFdC加/不加IFN-α对ACHN异种移植物的抑制作用明显更强。仅dFdC治疗出现了完全缓解（CR）。与单独使用dFdC治疗（20%；0）相比，额外给予IFN-α治疗缩短了肿瘤缓解开始时间，并提高了ACHN和SN12C肿瘤的CR率（分别为40%；7%）。与未治疗的动物相比，dFdC加IFN-α减少了肺转移的数量。在ACHN小鼠中，dFdC加/不加IFN-α显著延长了生存期，在SN12C小鼠中，dFdC加IFN-α或VBL加IFN-α显著延长了生存期。总之，实验数据证实，与VBL相比，dFdC是一种治疗人RCC的更优药物。在免疫缺陷的裸鼠中，联合IFN-α治疗可提高dFdC在肿瘤反应方面的疗效，因此强烈建议对转移性肾细胞癌患者进行临床研究。
