Lamborn K R, DeNardo G L, DeNardo S J, Goldstein D S, Shen S, Larkin E C, Kroger L A
Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco Medical Center, San Francisco, California 94143, USA.
Clin Cancer Res. 1997 Aug;3(8):1253-60.
This study was designed to evaluate dosimetric, pharmacokinetic, and other treatment-related parameters as predictors of outcome in patients with advanced B-lymphocytic malignancies. Fifty-seven patients were treated with radiolabeled Lym-1 antibody in early phase trials between 1985 and 1994. Logistic regression and proportional hazards models were used to evaluate treatment parameters for their ability to predict outcome, taking into account patient risk group based on Karnofsky performance status and serum lactic dehydrogenase. The occurrence of a partial or complete response (31 of 57 patients) and development of human antimouse antibody (HAMA) predicted improved survival using a time-dependent proportional hazards model. The final multivariate model for survival with parameters significant at P </= 0.05 included overall response and pretreatment risk group. Although some of the dosimetric and pharmacokinetic parameters were predictive in univariate analyses, only longer half-time of radionuclide in the blood showed any indication of improved prediction beyond that provided by the lactic dehydrogenase/Karnofsky performance status-based risk groups. Splenic volume, splenectomy, and malignant tissue Lym-1 reactivity were not contributory. In this patient group, the effect of radiolabeled Lym-1 treatment as indicated by measurable tumor response was associated with improved survival. Development of HAMA was also associated with improved survival, indicating that concern about HAMA should not preclude exploration of radioimmunotherapy. Although dosimetry has a role in determining safety based on dose to normal organs, when adjusted for baseline clinical features, dosimetric and pharmacokinetic parameters showed limited ability to improve outcome prediction.
本研究旨在评估剂量学、药代动力学及其他与治疗相关的参数，作为晚期B淋巴细胞恶性肿瘤患者预后的预测指标。1985年至1994年期间，57例患者在早期试验中接受了放射性标记的Lym-1抗体治疗。采用逻辑回归和比例风险模型，在考虑基于卡诺夫斯基体能状态和血清乳酸脱氢酶的患者风险组的情况下，评估治疗参数预测预后的能力。使用时间依赖性比例风险模型，部分或完全缓解（57例患者中的31例）的发生和人抗鼠抗体（HAMA）的产生预测了生存期的改善。最终的多变量生存模型中，P≤0.05时具有显著意义的参数包括总体缓解率和预处理风险组。尽管一些剂量学和药代动力学参数在单变量分析中具有预测性，但只有血液中放射性核素的半衰期延长显示出比基于乳酸脱氢酶/卡诺夫斯基体能状态的风险组提供的预测有任何改善的迹象。脾脏体积、脾切除术和恶性组织Lym-1反应性并无贡献。在该患者组中，可测量的肿瘤反应所表明的放射性标记Lym-1治疗效果与生存期改善相关。HAMA的产生也与生存期改善相关，这表明对HAMA的担忧不应妨碍对放射免疫治疗的探索。尽管剂量学在基于对正常器官的剂量确定安全性方面有作用，但在根据基线临床特征进行调整后，剂量学和药代动力学参数显示出改善预后预测的能力有限。
