Lee D J, Phillips T L, Coleman C N, Cosmatos D, Davis L W, Wasserman T H, Marcial V A, Rubin P
Johns Hopkins University, MD.
Int J Radiat Oncol Biol Phys. 1992;22(3):569-71. doi: 10.1016/0360-3016(92)90878-l.
In a Phase II study of etanidazole (SR 2508), the dose of 17 x 2 g/m2 (total drug dose: 34 g/m2) was tested in 33 patients and the toxicity was deemed acceptable. A Phase III trial is now in progress comparing conventional radiotherapy with conventional radiotherapy plus etandizole (2 g/m2 i.v. 30 to 60 min before radiotherapy each Monday, Wednesday, and Friday to 34 g/m2 in 17 doses) in patients with unresectable head and neck carcinomas. A recent analysis showed only 14.7% grade 1 and 3.9% Grade 2 peripheral neuropathy. In the initial study design, 133 evaluable patients per treatment arm could achieve an 80% level of power of detecting a 15% difference in local-regional control rates between the radiotherapy arm (25% local-regional control at 2 years) and the radiotherapy plus etanidazole arm (assuming a 40% rate). Allowing for 20 ineligible cases in each arm, a total number of 306 was required. An interim analysis showed that 27% of the patients assigned to radiotherapy plus etanidazole are receiving less than 14 doses of the drug. It is assumed that less than 14 drug doses will not produce any therapeutic gain, therefore, a true 40% local-regional control rate in the radiotherapy plus etanidazole arm will be observed as a 36% rate when analyzed by assigned treatment. Using this information, the study was modified to have an 80% level of power in detecting a difference between a 25% local-regional control rate in the radiotherapy group and a 36% rate in the radiotherapy plus etanidazole group. Allowing for a 10% patient ineligibility rate, 518 patients are required. With 12 patients entered per month, it is estimated that patient accrual to this study will continue through October 1991.
在一项关于乙硝唑（SR 2508）的II期研究中，对33例患者测试了17×2 g/m²（总药物剂量：34 g/m²）的剂量，其毒性被认为是可接受的。目前正在进行一项III期试验，比较常规放疗与常规放疗联合乙硝唑（放疗前每周一、三、五静脉注射2 g/m²，共30至60分钟，共17剂，总量达34 g/m²）对不可切除的头颈癌患者的疗效。最近的一项分析显示，只有14.7%为1级外周神经病变，3.9%为2级外周神经病变。在最初的研究设计中，每个治疗组133例可评估患者能够达到80%的检验效能，以检测放疗组（2年局部区域控制率为25%）和放疗联合乙硝唑组（假设为40%）之间局部区域控制率15%的差异。考虑到每组有20例不符合条件的病例，总共需要306例。一项中期分析显示，分配到放疗联合乙硝唑组的患者中有27%接受的药物剂量少于14剂。据推测，少于14剂药物不会产生任何治疗效果，因此，当按分配的治疗进行分析时，放疗联合乙硝唑组实际40%的局部区域控制率将被视为36%。利用这一信息，该研究进行了修改，以达到80%的检验效能，以检测放疗组25%的局部区域控制率与放疗联合乙硝唑组36%的局部区域控制率之间的差异。考虑到10%的患者不符合条件率，需要518例患者。每月有12例患者入组，预计该研究的患者招募将持续到1991年10月。
