Căinap Călin, Bochiş Ovidiu-Vasile, Vlad Cătălin, Popita Raluca, Achimaş-Cadariu Patriciu, Havasi Andrei, Vidrean Andreea, Dranca Alexandra, Piciu Andra, Constantin Anne-Marie, Tat Tiberiu, Dana Maniu, Crişan Ovidiu, Cioban Cosmin Vasile, Bălăcescu Ovidiu, Coza Ovidiu, Bălăcescu Loredana, Marta Monica Mihaela, Bota Madalina, Căinap Simona
"Prof Dr Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania.
Department of Oncology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Front Pharmacol. 2021 Mar 11;12:487316. doi: 10.3389/fphar.2021.487316. eCollection 2021.
Colorectal cancer (CRC) is the third most common cancer in Europe, with an annual increase in incidence ranging between 0.4 and 3.6% in various countries. Although the development of CRC was extensively studied, limited number of new therapies were developed in the last few years. Bevacizumab is frequently used as first- and second-line therapy for management of metastatic CRC (mCRC). The aim of this study is to present our experience with using bevacizumab beyond disease progression at different dosage levels in mCRC patients, in terms of overall survival, progression-free survival, time to treatment failure, and toxicities. We performed a consecutive retrospective analysis of patients with confirmed mCRC who were treated with bevacizumab at "Prof Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania. We included patients who had received bevacizumab as first- or second-line therapy and further stratified them according to the dose administered as a second-line (either standard dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, or double dose of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks-depending on the classical chemotherapy partner). All patients had received bevacizumab beyond progression (BYP) which is defined as continuing bevacizumab administration through second-line treatment despite disease progression. In each group, we evaluated the prognostic factors that influenced survival and treatment outcome. One hundred and fifty-one (151) patients were included in the study. Themedian age of patients receiving double dose bevacizumab (DDB) and standard dose bevacizumab (SDB) was 58 years (range 41-71) and 57 years (range 19-75), respectively. The median overall survival in the DDB group was 41 months (range 27-49) compared to 25 months (range 23-29) in the SDB group ( = 0.01 log-rank test). First-line oxaliplatin-based treatment was used more frequently regardless of group, while irinotecan-based more frequently used as a second-line treatment ( = 0.014). Both oxaliplatin- and irinotecan-based regimens were found to be suitable partners for BYP. Statistical analysis revealed that dose intensity, primary tumor location, and cumulative exposure to BYP had significant influence on survival. Doubling the dose of bevacizumab after first progression may improve survival in mCRC patients. Increasing bevacizumab dose intensity could override the prognostic impact of primary tumor location in patients receiving double the dose of bevacizumab after first disease progression.
结直肠癌（CRC）是欧洲第三大常见癌症，各国发病率年增长率在0.4%至3.6%之间。尽管对CRC的发展进行了广泛研究，但在过去几年中开发的新疗法数量有限。贝伐单抗经常被用作转移性CRC（mCRC）治疗的一线和二线疗法。本研究的目的是介绍我们在mCRC患者中不同剂量水平使用贝伐单抗超越疾病进展后的经验，包括总生存期、无进展生存期、治疗失败时间和毒性。我们对罗马尼亚克卢日-纳波卡“伊昂·基里库塔教授”肿瘤研究所确诊的接受贝伐单抗治疗的mCRC患者进行了连续回顾性分析。我们纳入了接受贝伐单抗作为一线或二线治疗的患者，并根据二线给药剂量（每2周5mg/kg标准剂量或每3周7.5mg/kg，或每2周10mg/kg或每3周15mg/kg双倍剂量，取决于经典化疗搭档）对他们进行进一步分层。所有患者均接受了超越疾病进展（BYP）的贝伐单抗治疗，BYP定义为尽管疾病进展仍在二线治疗中继续使用贝伐单抗。在每组中，我们评估了影响生存和治疗结果的预后因素。151名患者纳入研究。接受双倍剂量贝伐单抗（DDB）和标准剂量贝伐单抗（SDB）患者的中位年龄分别为58岁（范围41 - 71岁）和57岁（范围19 - 75岁）。DDB组的中位总生存期为41个月（范围27 - 49个月），而SDB组为25个月（范围23 - 29个月）（对数秩检验P = 0.01）。无论组别如何，一线基于奥沙利铂的治疗使用更为频繁，而基于伊立替康的治疗更常用于二线治疗（P = 0.014）。基于奥沙利铂和伊立替康的方案均被发现是BYP的合适搭档。统计分析显示，剂量强度、原发肿瘤部位和BYP的累积暴露对生存有显著影响。首次进展后将贝伐单抗剂量加倍可能改善mCRC患者的生存。增加贝伐单抗剂量强度可克服首次疾病进展后接受双倍剂量贝伐单抗患者中原发肿瘤部位的预后影响。
