Falcone A, Cianci C, Pfanner E, Ricci S, Lencioni M, Brunetti I, Giulianotti P C, Vannucci L, Mosca F, Conte P F
U.O. Oncologia Medica, Ospedale S. Chiara, Pisa, Italy.
Ann Oncol. 1996 Aug;7(6):601-5. doi: 10.1093/oxfordjournals.annonc.a010677.
Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in advanced renal cell carcinoma, with different dose-limiting toxic effects and antitumor synergism in experimental models. The main purpose of this phase II study was to assess the activity and toxic effects of a combination of FUDR and alpha 2b-IFN in metastatic renal cell carcinoma.
Metastatic renal cell carcinoma patients with measurable disease entered the study. FUDR was administered as a constant-rate continuous infusion for 14 days every 28 days at a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b 10 x 10(6) I.U. was administered intramuscularly 3 times per week.
Forty-two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN were administered. In 41 evaluable patients WHO grade III-IV toxic effects included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21 (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18-0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%) which lasted a median of 13 months (5.5-40+). Responses also occurred in liver (2), in patients pretreated with systemic therapy (5) and in patients who had other unfavourable prognostic characteristics (7). Median progression-free and survival times were 9 and 16 months, respectively.
In this study FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell carcinoma, showing promise also in patients with unfavourable prognostic characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be cumulative, but cumulative toxicity is also observed. These results require confirmation in randomised trials.
氟尿苷（FUDR）和α-干扰素（IFN）是晚期肾细胞癌的有效药物，在实验模型中具有不同的剂量限制性毒性作用和抗肿瘤协同作用。这项II期研究的主要目的是评估FUDR与α2b-IFN联合应用于转移性肾细胞癌的活性和毒性作用。
患有可测量疾病的转移性肾细胞癌患者进入本研究。FUDR每28天以恒定速率持续输注14天，起始日剂量为0.1mg/kg，若未出现WHO≥2级毒性反应，则在随后的每个周期中每天剂量递增0.025mg/kg。α2b干扰素10×10⁶IU每周肌肉注射3次。
42例患者进入研究，共给予272个周期的FUDR+α2b-IFN治疗。在41例可评估患者中，WHO III-IV级毒性反应包括恶心和呕吐（22%）、腹泻（32%）、口腔炎（12%）、疲劳（27%）和厌食（12%）。21例（50%）患者能够增加初始FUDR剂量；FUDR的中位剂量强度为0.35mg/kg/周（范围0.18-0.54）。在39例可评估患者中，观察到3例（7.5%）完全缓解和10例（25.5%）部分缓解（缓解率33%，95%置信区间（CI）19%-50%），缓解持续时间中位数为13个月（5.5-40+）。肝脏转移患者中出现缓解（2例），接受过全身治疗的患者中出现缓解（5例），具有其他不良预后特征的患者中出现缓解（7例）。无进展生存期和总生存期的中位数分别为9个月和16个月。
在本研究中，FUDR+α2b-IFN在转移性肾细胞癌中显示出令人感兴趣的活性，对具有不良预后特征的患者也显示出前景。FUDR和α2b-IFN的抗肿瘤活性似乎具有累积性，但也观察到累积毒性。这些结果需要在随机试验中得到证实。
