Figlin R A, Belldegrun A, Moldawer N, Zeffren J, deKernion J
Department of Medicine, University of California, School of Medicine, Los Angeles.
J Clin Oncol. 1992 Mar;10(3):414-21. doi: 10.1200/JCO.1992.10.3.414.
A phase II trial of interleukin-2 (IL-2) and interferon alfa (IFN-alpha) in metastatic renal cell carcinoma (RCCa) was conducted. A lower dosage of IL-2 was given via continuous intravenous (IV) infusion, a route with documented tumor activity associated with less toxicity, with the purpose of improving the therapeutic index of this treatment in an outpatient setting.
Thirty patients with metastatic RCCa were treated with the combination of IL-2 and IFN-alpha-2A. IL-2 was administered on days 1 through 4 of each treatment week, as a continuous IV infusion at a dose of 2 x 10(6) U/m2/d. IFN-alpha-2A was administered intramuscularly or subcutaneously on days 1 and 4 of each treatment week, at a dose of 6 x 10(6) U/m2/d. One treatment course included 4 weeks of treatment followed by a 2-week rest. Patients received therapy as outpatients except for the first 4 days of treatment, cycle 1 only. All patients were assessable for toxicity and response assessment. A total of 105 courses of therapy were administered, 51% at full dose.
Sixteen patients experienced toxicities resulting in dosage modification. The major treatment-limiting toxicities were gastrointestinal, neurologic, and fatigue. Nine patients (30%) had partial remissions (PRs) with a median duration of responses of 12+ months. The median time to response was 11 weeks. Two partial responders whose sites of metastatic disease were renal fossa and mediastinal lymph nodes (LN), respectively, were found to have achieved a pathologic complete remission (pCR) after surgery. A third patient with a pCR of axillary LN was rendered into a surgical complete remission (sCR) with salvage nephrectomy. Median survival of patients obtaining a PR has not been reached with a median follow-up time of 19+ months.
IL-2 and IFN-alpha-2A is well tolerated in the outpatient treatment setting and demonstrates significant clinical activity against RCCa.
开展一项针对转移性肾细胞癌（RCCa）的白细胞介素-2（IL-2）和干扰素α（IFN-α）的II期试验。通过持续静脉输注给予较低剂量的IL-2，该给药途径具有已证实的肿瘤活性且毒性较小，目的是在门诊环境中提高这种治疗的治疗指数。
30例转移性RCCa患者接受IL-2和IFN-α-2A联合治疗。IL-2在每个治疗周的第1至4天给药，通过持续静脉输注，剂量为2×10⁶ U/m²/d。IFN-α-2A在每个治疗周的第1天和第4天通过肌肉注射或皮下注射给药，剂量为6×10⁶ U/m²/d。一个疗程包括4周治疗，随后休息2周。除了第1周期治疗的前4天，患者均作为门诊患者接受治疗。所有患者均可进行毒性评估和疗效评估。共进行了105个疗程的治疗，51%为全剂量治疗。
16例患者出现毒性反应导致剂量调整。主要的治疗限制性毒性为胃肠道、神经方面和疲劳。9例患者（30%）出现部分缓解（PRs），缓解持续时间中位数为12+个月。缓解的中位时间为11周。分别有2例部分缓解者，其转移病灶部位为肾窝和纵隔淋巴结（LN），术后达到病理完全缓解（pCR）。第3例腋窝LN达到pCR的患者通过挽救性肾切除术实现了手术完全缓解（sCR）。获得PR的患者的中位生存期尚未达到，中位随访时间为19+个月。
IL-2和IFN-α-2A在门诊治疗环境中耐受性良好，并显示出对RCCa具有显著的临床活性。
