Millward M J, Cantwell B M, Munro N C, Robinson A, Corris P A, Harris A L
University Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, UK.
Br J Cancer. 1993 May;67(5):1031-5. doi: 10.1038/bjc.1993.189.
To determine if the chemotherapy resistance of non-small cell lung cancer could be modified by oral verapamil, 72 patients were entered into a randomised trial of verapamil plus chemotherapy vs the same chemotherapy alone. Verapamil 480 mg day-1 was given for 3 days starting 24 h prior to chemotherapy which consisted of bolus vindesine 7 mg followed by ifosfamide/mesna 5 g m-2 over 24 h, followed by mesna alone for a further 8 h. Cycles were repeated every 3 weeks for up to six courses. Sixty-six patients were eligible for tumour response analysis and responses occurred in 41% of those randomised to chemotherapy plus verapamil and in 18% of those randomised to chemotherapy alone (P = 0.057). Median survival from start of treatment was significantly better in the verapamil arm (P = 0.02). Toxicity of the combination of chemotherapy plus verapamil was principally neurological and was manageable. Thus the addition of oral verapamil to vindesine/ifosfamide chemotherapy is feasible and in this study was associated with improved outcome. Further confirmation of these observations is required in non-small cell lung cancer, a tumour characterised by resistance to conventional chemotherapy.
为了确定口服维拉帕米是否能改变非小细胞肺癌的化疗耐药性,72例患者进入了一项维拉帕米联合化疗与单纯相同化疗的随机试验。在化疗前24小时开始给予维拉帕米480毫克/天,持续3天,化疗方案为静脉推注长春地辛7毫克,随后24小时内给予异环磷酰胺/美司钠5克/平方米,然后单独给予美司钠8小时。每3周重复一个周期,最多进行六个疗程。66例患者符合肿瘤反应分析条件,随机接受化疗加维拉帕米的患者中41%出现反应,随机接受单纯化疗的患者中18%出现反应(P = 0.057)。从治疗开始的中位生存期在维拉帕米组明显更好(P = 0.02)。化疗加维拉帕米联合治疗的毒性主要为神经毒性,且可控制。因此,在长春地辛/异环磷酰胺化疗中添加口服维拉帕米是可行的,在本研究中与改善预后相关。在以对传统化疗耐药为特征的非小细胞肺癌中,需要进一步证实这些观察结果。