试论吉非替尼治疗晚期复治的非小细胞肺癌的临床观察(2)
作者:佚名; 更新时间:2014-12-12
本文观察的8例患者服用吉非替尼最主要的毒副作用为Ⅰ、Ⅱ度的皮疹(5/8) 和Ⅰ、Ⅱ度腹泻(3/8)、 Ⅲ度腹泻(1/8),未见间质性肺炎和急性肺损伤,亦未见心、肝、肾功能损害等毒副作用。本观察发现吉非替尼对不同的远处转移部位有不同的效应,对两肺内的粟粒样播散的有效率高于其他脏器的转移,而且肺内播散仍在CR或PR时却出现了新的脑转移和骨转移部位。这说明吉非替尼对不同脏器或部位远处转移的抑制效应不完全一致,对肺内转移的抑制效应强于其他脏器或部位的转移灶,这可能与表皮生长因子在体内器官分布上差异有关,有待进一步研究。发生Ⅰ、Ⅱ度的皮疹有4例为PR病人,1例NC病人,出现皮肤毒性的患者预示疗效好于没有皮肤毒性的患者,由于我们的样本量小,其疗效有待进一步验证。吉非替尼的毒性和副作用显著小于细胞毒类化疗,能为已经过反复治疗后失败的患者耐受,它特别对粟粒样的肺内播散有更大的抑制作用,说明吉非替尼可能对微小的病灶,即血供佳,且每个肿瘤的负荷较小,可能产生更大的抑制作用。由此可考虑把它从第三线治疗推向第二线,甚至第一线的治疗[9]。用于根治性手术后,作为辅助治疗,以抑制可能已发生的远处微小转移,以期减少远处转移的发生率或延迟它们的发生时间。由于我们观察的病例数少,其疗效及毒副作用有待于进一步验证。
[参考文献]
[1]Jemal A, Thomas A, Murray T, et al. Cancer statistics,2002[J].CA Cancer J Clin, 2002,52(1):23-47.
[2]Herbst RS, MaddoxAM,Rothenberg ML,et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solidtumors: results of a phaseⅠtrial[J].J Clin Oncol, 2002,20(18)∶3815-3825.
[3]CiardielloF,CaputoR,Bianco R,et al.Antitumor effect and potentiationof cytotoxic drugs activityin human cancer cells by ZD-1839 (Iressa).an epidermal growth factor receptor selective tyrosine kinase inhibitor[J].Clin Cancer Res,2000,6(5):2053 .
[4]Mendelson J.Blockade of receptors for growth factors: an anticancer therapythe fourth annual Joseph H Burchenal American Association of Cancer Research Clinical Research Award Lecture[J].Clin Cancer Res,2000,6(3)∶747-753.
[5]Ryan PD,Chabner BA.On receptor inhibitors and chemotherapy[J].Clin Cancer Res,2000,6(12)∶4607-4609.
[6]Nakagawa K,Tamura T,Negoro S,et al.PhaseⅠpharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib('Iressa',ZD1839)in Japanese patients with solid m alignant tumors[J]. Ann Oncol,2003,14(6):922.
[7] Fukuoka M, Yano S, Giaccone G,et al.Multi-institutional randomized phase Ⅱtrial of gefitinib for previously treated patients with advancednon-small-cell lung cancer(The IDEALⅠTrial)[corrected][J].J Clin Oncol,2003,21(12):2237.
[8]Argiris A, Mittal N.Gefitinib as first-line, compassionate use therapy in patients with advanced non- small-cell lung cancer[J].Lung Cancer,2004,43(3):317-322.