Shulman K L, Stadler W M, Vogelzang N J
University of Chicago, Illinois, USA.
Urology. 1996 Feb;47(2):194-7. doi: 10.1016/S0090-4295(99)80414-2.
Treatment of patients with metastatic renal cell carcinoma with high-dose interleukin-2 (IL-2) administered as continuous intravenous (CIV) infusion or as bolus injection results in response rates of 15% to 30%; however, toxicities with these regimens have been severe. A trial in which CIV IL-2 was administered at high doses during days 1 to 5 and at reduced doses during days 10 to 20 reported less toxicity without a decrease in response rates. We treated a series of patients with this regimen and our experience is presented.
Seventeen patients with metastatic renal cell carcinoma were treated with IL-2 by CIV at a dose of 18 x 10(6) IU/m2/day for 5 days followed by 4 to 6 days of rest followed by 10 days of CIV IL-2 at a dose of 6 x 10(6) IU/m2/day. Five patients also received CT-1501R, a pentoxifylline derivative.
There was 1 partial responder (PR) and there were no complete responses. The patient with the PR had a 14 x 9 cm(2) renal tumor with metastases to lung, pancreas, and liver. A surgical resection induced a CR, but he relapsed 9 months later. Severe toxicities included hyponatremia (serum sodium of less than 123 mmol/L) (n=3), biopsy-proven cardiomyopathy (n=1), creatinine more than 4.5 mg/dL (n=7), and sudden death (n=1).
We conclude that high-dose CIV IL-2 therapy of renal cell carcinoma results in severe toxicity and cannot be recommended for general use. Alternatives need to be developed.
采用大剂量白细胞介素-2（IL-2）持续静脉输注（CIV）或推注治疗转移性肾细胞癌患者，有效率为15%至30%；然而，这些方案的毒性反应严重。一项试验中，在第1至5天给予大剂量CIV IL-2，第10至20天给予减量，结果显示毒性反应较轻且有效率未降低。我们采用该方案治疗了一系列患者，并介绍我们的经验。
17例转移性肾细胞癌患者接受IL-2 CIV治疗，剂量为18×10⁶IU/m²/天，持续5天，随后休息4至6天，接着给予10天的CIV IL-2，剂量为6×10⁶IU/m²/天。5例患者还接受了己酮可可碱衍生物CT-1501R治疗。
有1例部分缓解者（PR），无完全缓解者。该PR患者有一个14×9 cm²的肾肿瘤，伴有肺、胰腺和肝转移。手术切除后达到完全缓解（CR），但9个月后复发。严重毒性反应包括低钠血症（血清钠低于123 mmol/L）（n = 3）、活检证实的心肌病（n = 1）、肌酐超过4.5 mg/dL（n = 7）和猝死（n = 1）。
我们得出结论，大剂量CIV IL-2治疗肾细胞癌会导致严重毒性反应，不推荐常规使用。需要开发替代方案。
