伦伐替尼治疗晚期肝细胞癌相关副作用及症状群管理的临床意义

Clinical significance of the management of adverse events and symptom cluster associated with advanced hepatocellular carcinoma after lenvatinib treatment

目的观察晚期肝细胞癌(HCC)患者接受分子靶向药物伦伐替尼治疗后出现的相关症状及症状群,探讨症状、症状群管理对减少3级以上相关不良事件和不良事件导致停止治疗的临床意义。方法纳入2017年5月-2018年12月在解放军总医院第五医学中心接受伦伐替尼治疗的晚期HCC患者98例。依据美国国立癌症研究所药物相关毒性判定标准,观察伦伐替尼相关副作用;以症状或症状群管理减少相关不良事件导致伦伐替尼剂量减少或中断或终止治疗例数为主要终点。结果 98例患者完成了全部观察,伦伐替尼相关副作用发生率> 20%,依次为高血压(42. 9%)、腹泻(33. 7%)、肝性脑病(30. 6%)、食欲减退(30. 6%)、蛋白尿(25. 5%)、疲乏(25. 5%)、手足综合征(22. 4%)、声音嘶哑(20. 4%)、体质量下降(20. 4%);3或4级不良反应发生54例(55. 1%),常见3级副作用是高血压(8. 2%),次之肝性脑病(6. 1%);4级不良反应发生1例(1%)。常见症状群依次为高血压蛋白尿症状群(56. 1%)、消化道综合征(50%)和疼痛综合征(36. 7%)。经过症状或症状群管理使相关不良事件导致伦伐替尼剂量减少或中断41例(41. 8%),终止治疗4例(4. 1%),低于REFLECT研究的52. 9%和8. 8%。结论伦伐替尼常见相关副作用是高血压和腹泻;高血压蛋白尿症状群、消化道综合征和疼痛综合征是主要症状群,症状群管理是降低不良事件导致终止分子靶向药物治疗的有效手段。

Objective To investigate the symptoms and symptom clusters in patients with advanced hepatocellular carcinoma( HCC) receiving molecular-targeted therapy with lenvatinib,as well as the clinical significance of the management of symptoms and symptom clusters in reducing lenvatinib-related grade 3 or above adverse events( AEs) and AEs leading to treatment termination. Methods A total of 98 patients with advanced HCC who were treated with lenvatinib in The Fifth Medical Center of Chinese PLA General Hospital from May 2017 to December 2018 were enrolled. The AEs associated with lenvatinib were observed according to National Cancer Institute Common Toxicity Criteria,and the primary endpoint was the number of cases with a reduced dose or interruption of lenvatinib or treatment termination due to lenvatinib-related AEs after the management of symptoms or symptom clusters. Results All 98 patients completed the whole procedure.As for the lenvatinib-related AEs with an incidence rate of > 20%,hypertension had the highest incidence rate of 42. 9%,followed by diarrhea( 33. 6%),hepatic encephalopathy( 30. 6%),anorexia( 30. 6%),proteinuria( 25. 5%),fatigue( 25. 5%),hand-foot syndrome( 22. 4%),hoarseness( 20. 4%),and weight loss( 20. 4%). The incidence rate of grade 3 or 4 AEs was 55. 1%( 54/98);the most common grade 3 AEs were hypertension( 8. 2%) and hepatic encephalopathy( 6. 1%),and grade 4 AE was observed in 1 patient( 1%). The most common symptom clusters included hypertensive proteinuria( 56. 1%),digestive tract syndrome( 50%),and pain syndrome( 36. 7%). Among the 98 patients,41( 41. 8%) had a reduced dose or interruption of lenvatinib due to lenvatinib-related AEs after the management of symptoms and symptom clusters and 4( 4. 1%) experienced treatment termination,which was lower than the percentages of 52. 9% and 8. 8% in the REFLECT study. Conclusion Hypertension and diarrhea are common AEs associated with lenvatinib. Hypertensive proteinuria,digestive tract syndrome,and pain syndrome are the main symptom clusters. Symptom cluster management is an effective means to reduce lenvatinib-related AEs leading to treatment termination.