Radiation Oncology, Zurich University Hospital, University of Zurich, Zurich, Switzerland.
Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):126-32. doi: 10.1016/j.ijrobp.2010.01.048. Epub 2010 Jun 18.
To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC).
In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m(2) (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity.
Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions.
Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.
评估吉非替尼（ZD1839，易瑞沙）联合放疗（RT）或顺铂（CDDP）同期放化疗（CRT）治疗晚期非小细胞肺癌（NSCLC）的可行性和耐受性。
这是一项多中心的 I 期研究，5 例不可切除的 NSCLC 患者在接受 63 Gy 放疗（第 1 步）前 1 周开始每天服用 250mg 吉非替尼。首次安全性分析后，9 例患者每天接受 250mg 吉非替尼联合 CRT，即放疗加每周 35mg/m² CDDP（第 2 步）。吉非替尼的使用时间最长为 2 年，直至疾病进展或出现毒性。
两步研究共评估了 14 例患者。第 1 步（5 例仅接受吉非替尼和 RT）中未见肺部毒性，无剂量限制性毒性（DLT）。不良反应为皮肤和皮下组织反应，仅限于 1-2 级。第 2 步中，9 例患者中有 2 例（22.2%）出现 DLT。1 例患者出现呼吸困难和与中性粒细胞减少性肺炎相关的脱水，另 1 例患者出现肝酶升高。在两步联合中，14 例患者中有 5 例（35.7%）出现 1 次或多次治疗中断。
吉非替尼（每日 250mg）联合放疗和 CDDP 治疗 III 期 NSCLC 是可行的，但 CDDP 可能会增加毒性。吉非替尼作为一线治疗与 RT 联合应用对生存和疾病控制的影响仍有待确定。
