Mantovani G, Bianchi A, Curreli L, Ghiani M, Santona M C, Proto E, Puxeddu P
Department of Medical Oncology, University of Cagliari, Italy.
Biotherapy. 1994;8(2):91-8. doi: 10.1007/BF01878492.
We carried out a pilot nonrandomized phase II study to compare the neo-adjuvant chemotherapic regimen with cisplatin, 5-FU and vinorelbine with the same combination plus s.c. IL 2 in advanced head and neck squamous cell carcinoma (HNSCC). The primary goals of the trial were to evaluate the feasibility and response rates of the two regimens. The study design consisted of a patient's assignment to either of the two following arms: Arm A: Cisplatin 80 mg/m2 i.v. on day 1; 5-FU 600 mg/m2 i.v. on days 2-5; and vinorelbine 20 mg/m2 i.v. on days 2 and 8, Arm B: the same chemotherapic regimen plus recombinant IL 2 (Proleukin, Eurocetus) 9 MIU s.c. daily from day 9 to 13 and from day 16 to 20 for every cycle. From March 1993 to November 1993 twenty three patients with Stage III-IV HNSCC were enrolled in the study. Patients could be evaluated for response to treatment if they had received at least 2 complete cycles of therapy. The overall response rate (ORR) was 63% in Arm A and 100% in Arm B. The differences for ORR and CR rates were statistically significant in favor of Arm B. The analysis for each of the three drugs included in the chemotherapy schedule shows that both the actually received average dose-intensity and the actually delivered average cumulative doses/patient were higher for Arm B (chemo-plus IL 2 therapy) (approximately 80% of programmed dose-intensity) than for Arm A (approximately 70% of programmed dose-intensity). Both the actually received average dose-intensity and the actually delivered average cumulative doses/patient for IL 2 were more than 80%. In both arms the most frequent side effects were myelosuppression, phlebitis and electrolyte disturbances. There were 2 toxic deaths, 1 in Arm A and 1 in Arm B, both for hematologic toxicity. Our "pilot" study suggests that the combination of cisplatin, 5-FU, vinorelbine plus IL 2 is a highly active, but rather toxic, neo-adjuvant treatment in advanced HNSCC with very high ORR and CR rates.
我们开展了一项非随机的II期试验性研究，以比较顺铂、5-氟尿嘧啶和长春瑞滨组成的新辅助化疗方案与相同组合加皮下注射白细胞介素-2（IL-2）方案在晚期头颈部鳞状细胞癌（HNSCC）中的疗效。该试验的主要目的是评估这两种方案的可行性和缓解率。研究设计包括将患者分配至以下两组之一：A组：第1天静脉注射顺铂80mg/m²；第2至5天静脉注射5-氟尿嘧啶600mg/m²；第2天和第8天静脉注射长春瑞滨20mg/m²；B组：相同的化疗方案加重组IL-2（Proleukin，欧洲赛特斯公司），每个周期从第第9至13天以及第16至20天每天皮下注射9MIU。从1993年3月至1993年11月，23例III-IV期HNSCC患者入组该研究。如果患者接受了至少2个完整周期的治疗，则可评估其对治疗的反应。A组的总缓解率（ORR）为63%，B组为100%。ORR和完全缓解（CR）率的差异具有统计学意义，有利于B组。对化疗方案中包含的三种药物中的每一种进行分析表明，B组（化疗加IL-2治疗）实际接受的平均剂量强度和实际给予每位患者的平均累积剂量均高于A组（分别约为计划剂量强度的80%和70%）。IL-2实际接受的平均剂量强度和实际给予每位患者的平均累积剂量均超过80%。两组中最常见的副作用是骨髓抑制、静脉炎和电解质紊乱。有2例毒性死亡，A组1例，B组1例，均为血液学毒性。我们的“试验性”研究表明，顺铂、5-氟尿嘧啶、长春瑞滨加IL-2的联合方案是晚期HNSCC中一种活性高但毒性较大的新辅助治疗方法，具有非常高的ORR和CR率。
