Somer Robert A, Sherman Eric, Langer Corey J
Department of Medical Oncology, Cooper Medical Center, Cherry Hill, NJ, USA.
Clin Lung Cancer. 2008 Mar;9(2):102-5. doi: 10.3816/CLC.2008.n.015.
In a previous randomized phase II trial evaluating carboplatin and paclitaxel with or without bevacizumab in patients naive to chemotherapy with advanced non-small-cell lung cancer (NSCLC), median survival ranged from 53 weeks to 76 weeks. Sudden life-threatening hemoptysis occurred in 6 of 66 patients receiving chemotherapy and bevacizumab; 4 episodes were fatal, all in patients with squamous cell histology. Squamous histology and bevacizumab therapy were the only factors associated with life-threatening hemorrhage. ECOG 4599 (Eastern Cooperative Oncology Group 4599), a randomized phase III trial of paclitaxel and carboplatin with or without bevacizumab ultimately excluded patients with squamous histology as well as brain metastases, ongoing therapeutic anticoagulation/nonsteroidal anti-inflammatory drugs, antecedent hemoptysis, and performance status (PS) of 2.
We performed a retrospective analysis during a defined period to determine the proportion of patients with newly evaluated advanced NSCLC seen at Fox Chase Cancer Center (FCCC) who would have been eligible for ECOG 4599. We reviewed new thoracic oncology patient visits (n = 260) at FCCC scheduled with 6 medical oncologists from March 1, 2002, through August 8, 2002.
Forty-five patients had histology that made them ineligible (8 mesothelioma, 6 small-cell, 5 mixed histology, and 26 non-lung cancers). Of the remaining 215 patients with NSCLC, 8 had incomplete charts for review and 7 had stage I, 8 stage II, and 43 stage III NSCLC. Of the remaining 149 patients, 33 had received chemotherapy previously. Of the remaining 116, only 34 (29.3%) were eligible. Of 82 ineligible patients, 21 (25.6%) had PS > or = 2, 20 (24.3%) had central nervous system (CNS) metastases, 11 (13.4%) had squamous histology, 9 (10.9%) had therapeutic anticoagulation, and 21 (25.6%) had > or = 2 criteria (11 PS > or = 2/squamous histology; 3 PS > or = 2/CNS involvement; 2 PS > or = 2/anticoagulation, 2 CNS metastasis/anticoagulation, 2 PS > or = 2/squamous histology/anticoagulation, 1 PS > or = 2/squamous histology/CNS metastasis). Of 34 eligible patients, only 6 (17.6%) enrolled in the trial.
Based on the data reviewed, > 70% of patients who might otherwise have been eligible for standard advanced NSCLC trials were not candidates for ECOG 4599. Outcome with respect to this study must be interpreted in the context of eligibility restrictions.
在一项先前的随机II期试验中，对晚期非小细胞肺癌（NSCLC）初治患者使用卡铂和紫杉醇联合或不联合贝伐单抗进行评估，中位生存期为53周至76周。在接受化疗和贝伐单抗治疗的66例患者中，有6例发生了危及生命的突发性咯血；4例死亡，均为鳞状细胞组织学类型的患者。鳞状细胞组织学类型和贝伐单抗治疗是与危及生命的出血相关的唯一因素。东部肿瘤协作组4599（ECOG 4599）试验是一项关于紫杉醇和卡铂联合或不联合贝伐单抗的随机III期试验，最终排除了鳞状细胞组织学类型患者以及有脑转移、正在进行治疗性抗凝/使用非甾体抗炎药、既往有咯血史和体能状态（PS）为2的患者。
我们在规定时期内进行了一项回顾性分析，以确定在福克斯蔡斯癌症中心（FCCC）新评估的晚期NSCLC患者中符合ECOG 4599试验条件的患者比例。我们回顾了2002年3月1日至2002年8月8日期间FCCC安排6名医学肿瘤学家诊治的新的胸部肿瘤患者就诊情况（n = 260）。
45例患者因组织学类型不符合条件（8例间皮瘤、6例小细胞癌、5例混合组织学类型和26例非肺癌）。在其余215例NSCLC患者中，8例病历不完整无法进行评估，7例为I期、8例为II期、43例为III期NSCLC。在其余149例患者中，33例曾接受过化疗。在其余116例患者中，只有34例（29.3%）符合条件。在82例不符合条件的患者中，21例（25.6%）PS≥2，20例（24.3%）有中枢神经系统（CNS）转移，11例（13.4%）为鳞状细胞组织学类型，9例（10.9%）正在进行治疗性抗凝，21例（25.6%）有≥2条不符合标准的情况（11例PS≥2/鳞状细胞组织学类型；3例PS≥2/CNS受累；2例PS≥2/抗凝，2例CNS转移/抗凝，2例PS≥2/鳞状细胞组织学类型/抗凝，1例PS≥2/鳞状细胞组织学类型/CNS转移）。在34例符合条件的患者中，只有6例（17.6%）参加了该试验。
根据所回顾的数据，原本可能符合标准晚期NSCLC试验条件的患者中，超过70%不符合ECOG 4599试验条件。必须在符合条件的限制背景下解释本研究的结果。
