羟基喜树碱联合异环磷酰胺治疗铂类耐药的非小细胞肺癌的临床研究

Hydroxycamptothecine and ifosfamide as second-line therapy in non-small cell lung cancer after prior treatment with platinum-based regimens

背景与目的 肿瘤细胞对铂类药物的耐药是非小细胞肺癌化疗失败的重要因素之一。研究和 探讨抑制或/和逆转肺癌多药耐药的有效药物和化疗方案是肺癌临床研究的热点课题。本研究的目的是比较 羟基喜树碱(HCPT)联合异环磷酰胺(IFO)治疗铂类耐药的NSCLC的疗效和毒性反应。方法 2002年6月 至2003年12月,入组NSCLC69例,予滴注HCPT6～8mg/m2,第1～5天,IFO1.2mg/m2,第1～3天,异 环磷酰胺使用后第0、4、8小时给予美安解毒。每21天为一周期。疗效及毒性评定按照WHO标准。结果 53例可评价疗效,无完全缓解者,部分缓解6例,稳定21例,进展26例,总有效率为11.3%(6/53),临床受益 率为50.9%(27/53)。化疗后PS评分显著提高。所有63例患者均可评价毒性反应,主要表现为不同程度的 骨髓抑制,其中白细胞降低发生率为85.5%(59/69),Ⅲ+Ⅳ度下降达17.3%(12/69);Ⅲ度血小板下降为 5.9%(4/69),无Ⅳ度毒性;Ⅲ度血红蛋白下降5.9%(4/69),无Ⅳ度毒性。脱发明显,达87.0%。结论 羟基 喜树碱联合异环磷酰胺治疗铂类耐药的NSCLC有效,不良反应可耐受,安全性高,患者可接受。

Background and objective Multiple drug-resistance to platinum is one of important influencing factors failure to chemotherapy in the treatment of non-small cell lung cancer (NSCLC). To study and explore the effective chemotherapy drugs and chemotherapeutic regimens inhibiting or reversing multiple drug-resistance is the popular problem in lung cancer clinic. The aim of this study is to evaluate the chemotherapeutic response and toxicities of combination of hydroxycamptothecine (HCPT) and ifosfamide (IFO) in patients with relapsed NSCLC after pretreatment with platinum-based regimens. Methods Patients with NSCLC, performance status (PS) < or =2, with history of prior platinum-based chemotherapy and without impaired haematopoietic and organ function were eligible. Chemotherapy was administered as follows: HCPT 6--8mg/m 2 from 1st to 5th day, IFO 1.2mg/m 2 from the 1st to 3rd day which was recycled every 3 weeks. Results From June 2002 to December 2003, 69 patients were enrolled and 53 were evaluable for response and all 69 for toxicity. The total response rate was 11.3% (6/53), stable disease was 39.6% (21/53) and progressive disease was 49.1% (26/53). The main side-effect was haematological toxicity, with grade Ⅲ--Ⅳ (G3--4) neutropenia in 12 patients, G3 thrombocytopenia and anemia in 4 and 4 patients respectively. Non-hematological toxicities were negligible. Alopecia rate was 87.0%. Conclusion The combination of HCPT and IFO is a tolerable and effective combination regimen to apply in the treatment of cisplatin-pretreated NSCLC patients.