Donaldson J T, Keane T E, Poulton S H, Walther P J
Department of Surgery/Urology, Duke University School of Medicine, Durham, NC.
Urol Res. 1990;18(4):245-50. doi: 10.1007/BF00294766.
The combination of tumor necrosis factor (TNF) and etoposide (ETP) was evaluated for potential cytotoxic efficacy against a human renal cell carcinoma xenograft using an in vivo assay employing an athymic mouse host with tumor implanted a the subrenal capsule site. Both antitumor efficacy (relative survival or RTS) and toxicity (weight loss) of TNF and ETP alone and in combination were evaluated. While TNF and ETP alone were mildly inhibitory (RTS 90% and 71%, respectively), the combination caused marked tumor inhibition (45% of controls). Host toxicity encountered with the combination did not exceed the toxicity associated with ETP alone, suggesting that the therapeutic index may have been augmented. It is concluded that enhanced antitumor activity without substantial augmentation of toxicity is observed with this combination, providing a rationale for further evaluation of tumor necrosis factor-based regimens for the treatment of advanced renal carcinoma.
使用无胸腺小鼠宿主，在肾被膜下植入肿瘤的体内试验中，评估了肿瘤坏死因子（TNF）和依托泊苷（ETP）联合使用对人肾细胞癌异种移植物的潜在细胞毒性疗效。评估了单独使用和联合使用TNF和ETP的抗肿瘤疗效（相对存活率或RTS）和毒性（体重减轻）。虽然单独使用TNF和ETP有轻度抑制作用（RTS分别为90%和71%），但联合使用导致明显的肿瘤抑制（为对照组的45%）。联合使用时所遇到的宿主毒性不超过单独使用ETP时的毒性，这表明治疗指数可能得到了提高。得出的结论是，该联合使用方案观察到增强的抗肿瘤活性且毒性没有大幅增加，这为进一步评估基于肿瘤坏死因子的方案治疗晚期肾癌提供了理论依据。
