长春花碱与γ干扰素联合或不联合13 - 顺式维甲酸用于晚期肾细胞癌患者。两项II期临床试验结果

Vinblastine and interferon-gamma combination with and without 13-cis retinoic acid for patients with advanced renal cell carcinoma. Results of two phase II clinical trials.

作者信息

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

机构信息

Medical Oncology Department, Hygeia Hospital, Athens, Greece. ParisKosmidis/Hygeia/

出版信息

Oncology. 2002;63(2):130-8. doi: 10.1159/000063806.

DOI:10.1159/000063806

PMID:12239447

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。