Bacoyiannis C, Dimopoulos M A, Kalofonos H P, Nicolaides C, Aravantinos G, Bafaloukos D, Samelis G, Onyenadum A, Kiamouris Ch, Skarlos D, Pavlidis N, Triantafillidis A, Kosmidis P
Medical Oncology Department, Hygeia Hospital, Athens, Greece. ParisKosmidis/Hygeia/
Oncology. 2002;63(2):130-8. doi: 10.1159/000063806.
The aim of this study is firstly to determine the response rates and toxicity of two regimens containing vinblastine (VBL) in combination with interferon-gamma (IFN-gamma) in the treatment of patients with advanced renal cell carcinoma (RCC), and secondly to evaluate the additional efficacy of 13-cis retinoic acid (13-CRA) in RCC.
Twenty-nine patients were included in the first trial (Trial 1) and 40 in the second one (Trial 2). The therapy given in Trial 1 consisted of VBL 0.15 mg/kg i.v. every 2 weeks and IFN-gamma 100 microg s.c. 3 times weekly. In Trial 2, the therapy consisted of the same two drugs, in the same doses, plus oral 13-CRA 40 mg/day.
In Trial 1 there were 3 (10.3%) patients with complete response, 3 (10.3%) patients with partial response, 8 (27.6%) patients with stable disease and 15 (51.7%) patients with progressive disease. In Trial 2, there was no complete response, however, 3 (7.5%) patients had partial response. Additionally, 15 (37.5%) patients maintained stable disease and 14 (35%) patients had progressive disease. In Trial 1, the median survival was 12.56 months (95% CI, 6.8-18.3, range 0.59-42.49) and the median time to progression was 3.21 months (95% CI, 1.7-4.7, range 0.03-42.49). In Trial 2, the median survival was 9.54 months (95% CI, 5.9-13.1, range 0.43-24.1) and the median time to progression was 3.9 months (95% CI, 0.8-7, range 0.26-24.1). In Trial 1, granulocytopenia grade 3 and 4 appeared in 5 (17.2%) patients and anaemia grade 3 in 1 (3.4%) patient. In Trial 2, there were grade 3 toxicities, as granulocytopenia in 5 (12.5%) patients, anemia in 4 (10.0%) patients, stomatitis in 3 (7.5%) patients, fatigue/malaise in 3 (7.5%) patients and 1 (2.5%) had diarrhea. No toxic deaths occurred in both studies.
The use of IFN-gamma does not enhance the low response of VBL-based chemotherapy. The additional administration of 13-CRA with the combination of VBL and IFN-gamma does not add to the efficacy of this combination in patients with advanced renal cell carcinoma. New active agents are needed to treat patients with this disease.
本研究的目的，一是确定两种含长春碱（VBL）联合γ干扰素（IFN-γ）的方案治疗晚期肾细胞癌（RCC）患者的缓解率和毒性，二是评估13-顺式维甲酸（13-CRA）对RCC的额外疗效。
第一项试验（试验1）纳入29例患者，第二项试验（试验2）纳入40例患者。试验1的治疗方案为每2周静脉注射VBL 0.15 mg/kg，每周皮下注射IFN-γ 100 μg，共3次。试验2的治疗方案为相同的两种药物、相同剂量，加口服13-CRA 40 mg/天。
试验1中，3例（10.3%）患者完全缓解，3例（10.3%）部分缓解，8例（27.6%）疾病稳定，15例（51.7%）疾病进展。试验2中，无完全缓解患者，但有3例（7.5%）部分缓解。此外，15例（37.5%）患者疾病稳定，14例（35%）疾病进展。试验1中，中位生存期为12.56个月（95%CI，6.8 - 18.3，范围0.59 - 42.49），中位疾病进展时间为3.21个月（95%CI，1.7 - 4.7，范围0.03 - 42.49）。试验2中，中位生存期为9.54个月（95%CI，5.9 - 13.1，范围0.43 - 24.1），中位疾病进展时间为3.9个月（95%CI，0.8 - 7，范围0.26 - 24.1）。试验1中，5例（17.2%）患者出现3级和4级粒细胞减少，1例（3.4%）患者出现3级贫血。试验2中，出现3级毒性反应，5例（12.5%）患者粒细胞减少，4例（10.0%）患者贫血，3例（7.5%）患者口腔炎，3例（7.5%）患者疲劳/不适，1例（2.5%）患者腹泻。两项研究均未发生毒性死亡。
使用IFN-γ并未增强基于VBL的化疗的低缓解率。VBL与IFN-γ联合使用时额外给予13-CRA，并未增加该联合方案对晚期肾细胞癌患者的疗效。治疗该疾病的患者需要新的活性药物。
