Bachelot T, Ray-Coquard I, Catimel G, Ardiet C, Guastalla J P, Dumortier A, Chauvin F, Droz J P, Philip T, Clavel M
Département de Cancérologie Médicale, Centre Léon Bérard, Lyon, France.
Ann Oncol. 2000 Feb;11(2):151-6. doi: 10.1023/a:1008368319526.
Patients with advanced solid tumors may be included in phase I clinical trials. In such studies, the benefit expected is generally lower than the likelihood of toxicity and may even be non-existent if the patient's life expectancy is too short. This study was performed to identify prognostic variables for toxicity and survival in patients who participate in phase I clinical trials.
One hundred fifty-four patients treated on a phase I clinical trial in our institute were evaluated retrospectively. Univariable and multivariable analyses of patients' characteristics were undertaken to determine their effects on the probability of grade 3 and 4 toxicity and on survival.
Grade 3 or 4 toxicity was experienced by 56 patients (36%): dosage level at entry (P < 0.001) and age over 65 years (P = 0.03) were independently associated with the risk of toxicity. Median overall survival was 5 months. The multivariable analysis identified performance status 2 or 3 (P < 0.001) and lactate dehydrogenase levels greater than 600 UI (P < 0.001) as independent adverse prognostic variables for overall survival. Using these two parameters, we determined a prognostic index which allowed us to discriminate three risk groups of patients with an observed median survival of 8.5, 4.5 and 1.5 months, respectively.
Subgroups with different survival expectancy can be identified among patients who are eligible for phase I clinical trials. If confirmed, the proposed prognostic model may be useful for therapeutic decision making in palliative oncology.
晚期实体瘤患者可能被纳入I期临床试验。在此类研究中，预期的获益通常低于出现毒性反应的可能性，并且如果患者预期寿命过短，获益甚至可能不存在。本研究旨在确定参与I期临床试验患者毒性反应和生存情况的预后变量。
对在我院进行I期临床试验治疗的154例患者进行回顾性评估。对患者特征进行单变量和多变量分析，以确定其对3级和4级毒性反应概率及生存情况的影响。
56例患者（36%）出现3级或4级毒性反应：入组时的剂量水平（P<0.001）和65岁以上年龄（P = 0.03）与毒性反应风险独立相关。总生存期中位数为5个月。多变量分析确定体能状态为2或3（P<0.001）以及乳酸脱氢酶水平大于600 UI（P<0.001）为总生存情况的独立不良预后变量。使用这两个参数，我们确定了一个预后指数，据此可将患者分为三个风险组，观察到的中位生存期分别为8.5个月、4.5个月和1.5个月。
在符合I期临床试验条件的患者中可识别出具有不同预期生存期的亚组。如果得到证实，所提出的预后模型可能有助于姑息肿瘤学的治疗决策。
