May M, Helke C, Bock M, Hoschke B
Urologische Klinik, Carl-Thiem-Klinikum, Cottbus.
Urologe A. 2004 Sep;43(9):1111-9. doi: 10.1007/s00120-004-0626-2.
The prognosis for patients with metastatic renal cell carcinoma (RCC) remains unsatisfactory to date. Combined immunochemotherapy (ICT) strives for a synergistic effect avoiding a substantial increase of therapy-related adverse events. The combination therapy regimes consisting of either interferon-alpha-2a/vinblastine (IFN-alpha2a/VBL) or interferon-alpha-2a/interleukin-2/5-fluorouracil (IFN-alpha2a/IL-2/5-FU) demonstrated objective remission rates, surpassing the results obtained with the administration of single immunotherapeutic agents. Despite the data from a recently published study, the role of these two therapy combinations did not seem clearly defined. Therefore, we compared the impact of IFN-alpha2a/VBL and IFN-alpha2a/IL-2/5-FU on remission and survival as well as the safety profile in a retrospective study in patients with metastatic RCC. In a retrospective single-center study, 105 patients with metastatic RCC having received treatment between 1992 and 2002 with either s.c. IFN-alpha2a/ i.v. VBL ( n=70, group 1) or s.c. IFN-alpha2a/ s.c. IL-2/ i.v. 5-FU ( n=35, group 2) were evaluated. At a median follow-up of 17 months, remission and survival rates as well as the toxicity profiles of the respective groups were documented and compared. The median age throughout the entire patient population was 61 years. Patients in the IFN-alpha2a/VBL group reached a median overall survival of 20 months compared to 17 months for the patients in the IFN-alpha2a/IL-2/5-FU population ( p=0.850). The objective response rate in the first patient group reached 25.7%, whereas the tumor remission rate of group 2 amounted to 22.9% ( p=0.680). Patients showing an objective response reached a significantly higher survival rate than patients without response reaction (median survival was 36 vs 10 months, p=0.0001). The incidence of each therapy-induced adverse event was higher throughout the second treatment group. These differences were significant with respect to flu-like symptoms (85.7 vs 57.1%, p=0.003), grade 3/4 elevations of liver enzymes (14.3 vs 1.4%, p=0.007), nausea/vomiting (74.3 vs 50%, p=0.017), the severity of erythemas (74.3 vs 10%, p<0.001), and patients with lung edema (17.1 vs 2.9%, p=0.009). Eight patients discontinued the ICT, two of whom died of a myocardial infarction.Despite an overall limited prognosis, patients showing a tumor remission seem to benefit from ICT in terms of overall survival. While both treatment options offer comparable remission and survival rates, the IFN-alpha2a/VBL regimen induces fewer adverse events than the treatment with IFN-alpha2a/IL-2/5-FU.
迄今为止,转移性肾细胞癌(RCC)患者的预后仍不尽人意。联合免疫化疗(ICT)旨在实现协同效应,同时避免治疗相关不良事件大幅增加。由α-干扰素-2a/长春花碱(IFN-α2a/VBL)或α-干扰素-2a/白细胞介素-2/5-氟尿嘧啶(IFN-α2a/IL-2/5-FU)组成的联合治疗方案显示出客观缓解率,超过了单一免疫治疗药物给药所获得的结果。尽管有最近发表的一项研究的数据,但这两种治疗组合的作用似乎并未明确界定。因此,我们在一项针对转移性RCC患者的回顾性研究中,比较了IFN-α2a/VBL和IFN-α2a/IL-2/5-FU对缓解率、生存率以及安全性的影响。在一项回顾性单中心研究中,对1992年至2002年间接受过皮下注射IFN-α2a/静脉注射VBL(n = 70,第1组)或皮下注射IFN-α2a/皮下注射IL-2/静脉注射5-FU(n = 35,第2组)治疗的105例转移性RCC患者进行了评估。在中位随访17个月时,记录并比较了各组的缓解率、生存率以及毒性特征。整个患者群体的中位年龄为61岁。IFN-α2a/VBL组患者的中位总生存期为20个月,而IFN-α2a/IL-2/5-FU组患者为17个月(p = 0.850)。第一组患者的客观缓解率达到25.7%,而第二组的肿瘤缓解率为22.9%(p = 0.680)。显示出客观缓解的患者的生存率明显高于无反应的患者(中位生存期分别为36个月和10个月,p = 0.0001)。在整个第二个治疗组中,每种治疗引起的不良事件发生率都更高。在流感样症状(85.7%对57.1%,p = 0.003)、3/4级肝酶升高(14.3%对1.4%,p = 0.(此处原文有误,根据前文推测应为p = 0.007))、恶心/呕吐(74.3%对50%,p = 0.017)、红斑严重程度(74.3%对10%,p < 0.001)以及肺水肿患者(17.1%对2.9%,p = 0.009)方面,这些差异具有统计学意义。8例患者停止了ICT治疗,其中2例死于心肌梗死。尽管总体预后有限,但显示出肿瘤缓解的患者在总生存期方面似乎从ICT中获益。虽然两种治疗方案的缓解率和生存率相当,但IFN-α2a/VBL方案比IFN-α2a/IL-2/5-FU治疗引起的不良事件更少。