Ottaiano Alessandro, Mollo Ernesto, Di Lorenzo Giuseppe, Pisano Carmela, Di Maio Massimo, Barletta Emiddio, Pensabene Matilde, Segati Romana, Bullian Pierluigi, Nasti Guglielmo, Bryce Jane, Scala Stefania, Castello Giuseppe, Ascierto Paolo Antonio
Department of Medical Oncology, ULSS2, Santa Maria del Prato Hospital, via Bagnols Ceze, Feltre (BL), Italy.
Cancer Immunol Immunother. 2005 Jan;54(1):44-50. doi: 10.1007/s00262-004-0567-z.
To review the content and quality of prospective clinical trials of biotherapies in solid tumors.
Data were collected from the literature between 1990 and 2002 on general study characteristics, patient and disease factors, study methodology, and factors related to completeness of reporting. Quality of phase II studies was evaluated by an ad hoc questionnaire. Descriptive statistics, contingency tables, and the chi-square test were applied.
A total of 334 studies were selected, of which about three quarters were multicenter, with 42.5% reporting phase I, 42.2% phase II or I/II, and 11.9% phase III or II/III studies. Only 13.7% were randomized, and a study design emphasizing statistical analysis was lacking in as many as one third. The assessment of biological endpoints was stated as the primary or secondary goal in half of these studies. Melanoma (17.1%), renal carcinoma (11.1%), gastrointestinal neoplasms (11.1%), and lymphomas (6.3%) were the most studied diseases. Immunotherapies accounted for 182 studies; the remaining 152 reported other biotherapies. Patients with (1) advanced disease (P = 0.003), (2) heavily pretreated neoplasms (P < 0.0001), (3) poor performance status (PS < 2) (P < 0.0001), were more frequently enrolled in studies of biotherapy. Biotherapies were less frequently evaluated in phase III studies (7/152) compared with immunotherapies (33/182) (P < 0.0001). A statistical study design was more frequently identified in biotherapy trials (127/152) compared with immunotherapy trials (98/182) (P < 0.0001). Biological endpoints were less frequently evaluated in phase III studies in both biotherapies (100% no vs 0% yes) and immunotherapies (81.8% no vs 18.2% yes) (P = 0.01, for biotherapies; P < 0.0001, for immunotherapies). Phase I immunotherapy studies more frequently applied biological or molecular criteria for patient selection (41.1%) than phase II (29.3%) and III (3.1%) studies (P < 0.0001).
The very wide diversity in modalities of conducting and reporting clinical trials of biotherapies of solid tumors and the presence of some methodological pitfalls suggest that the methodological standards for conducting and publishing clinical trials in biotherapies should be improved to enhance the reliability of the body of published data.
回顾实体瘤生物治疗前瞻性临床试验的内容和质量。
收集1990年至2002年间文献中有关一般研究特征、患者和疾病因素、研究方法以及与报告完整性相关的因素的数据。通过一份专门设计的问卷对II期研究的质量进行评估。应用描述性统计、列联表和卡方检验。
共筛选出334项研究，其中约四分之三为多中心研究，42.5%报告为I期，42.2%为II期或I/II期，11.9%为III期或II/III期研究。只有13.7%为随机研究，多达三分之一的研究缺乏强调统计分析的研究设计。在这些研究中，有一半将生物终点评估作为主要或次要目标。黑色素瘤（17.1%）、肾癌（11.1%）、胃肠道肿瘤（11.1%）和淋巴瘤（6.3%）是研究最多的疾病。免疫治疗占182项研究；其余152项报告了其他生物治疗方法。患有（1）晚期疾病（P = 0.003）、（2）接受过大量预处理的肿瘤（P < 0.0001）、（3）体能状态差（PS < 2）（P < 0.0001）的患者更常被纳入生物治疗研究。与免疫治疗（33/182）相比，生物治疗在III期研究中评估得较少（7/152）（P < 0.0001）。与免疫治疗试验（98/182）相比，生物治疗试验（127/152）更常采用统计研究设计（P < 0.0001）。在生物治疗和免疫治疗的III期研究中，生物终点评估都较少（生物治疗：100%无vs 0%有；免疫治疗：81.8%无vs 18.2%有）（生物治疗P = 0.01；免疫治疗P < 0.0001）。I期免疫治疗研究比II期（29.3%）和III期（3.1%）研究更常应用生物或分子标准进行患者选择（41.1%）（P < 0.0001）。
实体瘤生物治疗临床试验的开展和报告方式存在极大差异，且存在一些方法学上的缺陷，这表明应提高生物治疗临床试验开展和发表的方法学标准，以增强已发表数据的可靠性。
