Gaddipati Himabindu, Fu Pingfu, Dowlati Afshin
Division of Hematology/Oncology, Case Western Reserve University and University Hospitals Case Medical Center and the Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH.
J Geriatr Oncol. 2011 Apr 1;2(2):142-146. doi: 10.1016/j.jgo.2011.01.001.
Phase I clinical trials play a crucial role in development of therapeutics for cancer patients. During phase I clinical trials common toxicities are delineated, dose limiting toxicities (DLT) are determined and a dose for phase II studies is recommended. However, reviews of the phase I population indicate a younger group of participants with a median age of 50-55. No data exists on the performance of octogenarians on phase I trials. Concerns for enrollment of this patient population, relates to presence of comorbidities and possibly altered pharmacokinetics in the setting of unknown potential toxicities. We present herein the largest review of octogenarians on phase I trials. Twenty-two octogenarian patients with a median age of 83 were enrolled on phase I clinical trials. More than 50% of them were chemotherapy-naïve most likely indicative of the fact that treating physicians believed standard therapy to be potentially toxic to this population. These 22 patients were otherwise matched in terms of performance status and other parameters to a control group of participants < 80. This includes a similar number of cycles administered. Patients ≥80 had a 3 fold higher rate of achieving DLT (p=0.06) compared to the control group enrolled at the same dose level. The toxicities observed include cardiovascular, gastrointestinal and infectious complications. Three patients were enrolled on molecular targeted treatments with no significant toxicities. We conclude that enrollment of patients ≥80 on phase I trials of chemotherapy agents is most likely associated with higher risk of DLT.
I期临床试验在癌症患者治疗药物的研发中起着至关重要的作用。在I期临床试验期间，要明确常见毒性，确定剂量限制毒性（DLT），并推荐II期研究的剂量。然而，对I期试验人群的综述表明，参与者群体较为年轻，中位年龄为50 - 55岁。目前尚无关于八旬老人在I期试验中表现的数据。对于该患者群体的入组问题，涉及到合并症的存在以及在潜在毒性未知的情况下可能改变的药代动力学。我们在此呈现了对八旬老人I期试验的最大规模综述。22名中位年龄为83岁的八旬老人患者参与了I期临床试验。其中超过50%的患者未曾接受过化疗，这很可能表明治疗医生认为标准疗法对该群体可能具有潜在毒性。这22名患者在体能状态和其他参数方面与年龄小于80岁的对照组相匹配。这包括给药周期数量相似。与在相同剂量水平入组的对照组相比，80岁及以上患者达到DLT的发生率高出3倍（p = 0.06）。观察到的毒性包括心血管、胃肠道和感染性并发症。三名患者参与了分子靶向治疗，未出现明显毒性。我们得出结论，80岁及以上患者参与化疗药物的I期试验很可能与更高的DLT风险相关。
