Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: A Hoosier Oncology Group phase II trial
Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: A Hoosier Oncology Group phase II trial
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DOI：
10.1016/j.lungcan.2005.12.002
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发表时间：
2006-04-01
期刊：
影响因子：
5.3
通讯作者：
Hanna, NH
中科院分区：
文献类型：
--
作者：
Moore, AM;Einhorn, LH;Hanna, NH
背景：吉非替尼在非小细胞肺癌（NSCLC）患者中表现出活性。临床试验尚未证明吉非替尼的反应与表皮生长因子受体（EGFR）过度表达之间的关系。虽然EGFR在小细胞肺癌（SCLC）中没有过度表达，但我们推测吉非替尼可能通过其他机制影响肿瘤生长。在NSCLC中有活性的药物通常在SCLC.Methods中也有效：主要目的是评估吉非替尼在化疗耐药和化疗敏感的小细胞癌患者中的临床控制率：完全缓解（CR）、部分缓解（PR）和疾病稳定（SD > 90天）。入选标准包括神经内分泌肿瘤（尤其是小细胞癌）的病理学证据、美国东部肿瘤协作组（ECOG）体能状态（PS）0-2、既往接受过1种或2种化疗方案治疗以及适当的终末器官功能。患者接受吉非替尼，250 mg p.o.结果：2003年4月至2004年3月，19例患者入选。小细胞肺癌占19例患者中的18例，1例患者患有转移性默克尔细胞癌。12例患者（63%）患有化学敏感性疾病，定义为既往化疗完成后3个月以上的进展; 7例（37%）患有化学难治性疾病; 13例（68%）既往接受过一种化疗方案。其他患者特征：平均年龄64岁（范围52-79岁）; ECOG PS 0/1/2=7/9/3，男：女=9：10。3级毒性包括：疲劳3例（15.8%），肺毒性3例（15.8%），高血糖或疼痛各1例（5.3%）。4例患者出现4级毒性：1例患者（5.3%）出现疲乏，3例患者（15.8%）出现呼吸困难。无患者发生3级或4级皮疹或腹泻。2例患者病情稳定（< 90天），17例患者病情进展为最佳缓解。本研究为两阶段设计，由于不符合第一阶段的持续标准，因此未进行第二阶段。中位至进展时间（TTP）为50天（95% CI = 21-58天）。1年总生存率为21%（95%CI = 6 ~ 45.6%.Conclusion：虽然吉非替尼对部分NSCLC患者有疗效，但对小细胞肺癌患者疗效不明显。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Background: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell, tung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC.Methods: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemoresistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects.Results: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2=7/9/3, M:F=9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (< 90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%).Conclusion: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer. (c) 2006 Elsevier Ireland Ltd. All rights reserved.