Tourani J M, Pfister C, Berdah J F, Benhammouda A, Salze P, Monnier A, Paule B, Guillet P, Chretien Y, Brewer Y, Di Palma M, Untereiner M, Malaurie E, Tadrist Z, Pavlovitch J M, Hauteville D, Mejean A, Azagury M, Mayeur D, Lucas V, Krakowski I, Larregain-Fournier D, Abourachid H, Andrieu J M, Chastang C
Unité d'Oncologie Médicale, Hôpital Laënnec, Paris, France.
J Clin Oncol. 1998 Jul;16(7):2505-13. doi: 10.1200/JCO.1998.16.7.2505.
We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%.
Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes.
This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04).
As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.
我们报告皮下注射Propeukin方案（SCAPP）II期试验的结果，该试验为一项针对肾细胞癌的门诊治疗，采用皮下注射白细胞介素-2（IL-2）、干扰素α-2a（IFN-α）并联合氟尿嘧啶（5-FU）。这项多中心试验的目的是确认IL-2、IFN-α和5-FU联合使用的缓解率大于20%。
转移性肾细胞癌患者纳入本研究。在为期10周的诱导治疗阶段，IL-2和IFN-α皮下注射，每周3次，共8周，剂量分别为18 MIU和9 MIU。在这8周期间，每周一静脉输注5-FU，剂量为750 mg，持续30分钟。评估后，有反应的患者或疾病稳定（SD）的患者接受维持治疗，直至疾病进展（PD）或出现不可接受的毒性。每个维持周期包括2周治疗，随后是3周休息期。治疗期间，IL-2和IFN-α皮下注射，每周3次，剂量分别为18 MIU和9 MIU。每周一静脉输注5-FU，剂量为750 mg，持续30分钟。
当第六次序贯分析显示该联合方案无益处时，本试验终止。诱导期结束时，62例患者中，12例（19%；95%置信区间[CI]，10%至31%）达到客观缓解，包括1例完全缓解（CR），16例疾病稳定，27例疾病进展。27例患者（43%）出现严重毒性，需要降低计划剂量（13例患者）、延迟治疗（8例患者）或终止治疗（6例患者）。17例患者接受维持治疗。1年和2年生存率估计分别为55%和33%。11例有三个预后不良因素的患者2年生存率为15%，51例最初无、有一个或两个预后不良因素的患者2年生存率为41%（P = 0.04）。
与其他最近发表的使用5-FU、IL-2和IFN-α的研究一样，转移性肾细胞癌患者的多中心SCAPP II期试验产生了严重毒性。这项序贯试验未能证实Atzpodien和Sella此前使用这三种药物联合方案所取得的良好结果。根据缓解率和生存率评估，其疗效接近皮下单独使用IL-2方案所观察到的结果。
