Dunkel Ira J, Shi Weiji, Salvaggio Kim, Marr Brian P, Brodie Scott E, Gobin Y Pierre, Abramson David H
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America; Department of Pediatrics, New York Presbyterian Hospital Weill Cornell Medical College, New York, NY, United States of America.
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
PLoS One. 2014 Oct 10;9(10):e108692. doi: 10.1371/journal.pone.0108692. eCollection 2014.
Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥ grade 3) neutropenia.
Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0.
54 cycles (29%) were associated with grade 3 (n = 43) or grade 4 (n = 11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33-12.73, p = 0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis.
Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.
动脉内化疗是眼内视网膜母细胞瘤一种有前景的治疗策略。中性粒细胞减少是最常见的全身毒性反应，在本研究中，我们旨在确定与严重（≥3级）中性粒细胞减少发生相关的危险因素。
回顾性分析2006年5月至2011年6月期间，对106例眼内视网膜母细胞瘤患者进行的前三个含美法仑动脉内化疗周期中的187个可评估周期。如果（1）在治疗后7至14天的间隔期有血细胞计数结果，且（2）未同时进行静脉化疗，则这些周期被认为是可评估的。通过《不良事件通用术语标准》第4.0版评估毒性。
54个周期（29%）与3级（n = 43）或4级（n = 11）中性粒细胞减少相关。多因素逐步逻辑回归显示，较高的美法仑剂量（>0.40 mg/kg）与所有3个周期中的严重中性粒细胞减少显著相关（第一个周期的比值比为4.11，95%置信区间为1.33 - 12.73，p = 0.01），但添加拓扑替康和/或卡铂则不然。在任何分析中，先前的全身化疗治疗与严重中性粒细胞减少风险均无关。
基于美法仑的动脉内化疗可导致严重中性粒细胞减少，尤其是当剂量大于0.40 mg/kg时。可能需要进行更大样本的进一步研究。
