Sud S, O'Callaghan C, Jonker C, Karapetis C, Price T, Tebbutt N, Shapiro J, Van Hazel G, Pavlakis N, Gibbs P, Jeffrey M, Siu L, Gill S, Wong R, Jonker D, Tu D, Goodwin R
Division of Medical Oncology, Department of Medicine, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON.
ncic Clinical Trials Group, Queen's University, Kingston, ON.
Curr Oncol. 2018 Dec;25(6):e516-e526. doi: 10.3747/co.25.4069. Epub 2018 Dec 1.
Adrenergic receptor stimulation is involved in the development of hypertension (htn) and has been implicated in cancer progression and dissemination of metastases in various tumours, including colon cancer. Adrenergic antagonists such as beta-blockers (bbs) demonstrate inhibition of invasion and migration in colon cancer cell lines and have been associated with decreased mortality in colorectal cancer (crc). We examined the association of baseline htn and bb use with overall (os) and progression-free survival (pfs) in patients with pretreated, chemotherapy refractory, metastatic crc (mcrc). We also examined baseline htn as a predictor of cetuximab efficacy.
Using data from the Canadian Cancer Trials Group co.17 study [cetuximab vs. best supportive care (bsc)], we coded baseline htn and use of anti-htn medications, including bbs, for 572 patients. The chi-square test was used to assess the associations between those variables and baseline characteristics. Cox regression models were used for univariate and multivariate analyses of os and pfs by htn diagnosis and bb use.
Baseline htn, bb use, and anti-htn medication use were not found to be prognostic for improved os. Baseline htn and bb use were not significant predictors of cetuximab benefit.
In chemorefractory mcrc, neither baseline htn nor bb use is a significant prognostic factor. Baseline htn and bb use are not predictive of cetuximab benefit. Further investigation to determine whether baseline htn or bb use have a similarly insignificant impact on prognosis in patients receiving earlier lines of treatment remains warranted.
肾上腺素能受体刺激参与高血压(HTN)的发生发展,并与包括结肠癌在内的多种肿瘤的癌症进展和转移扩散有关。β受体阻滞剂(BBs)等肾上腺素能拮抗剂可抑制结肠癌细胞系的侵袭和迁移,并与降低结直肠癌(CRC)死亡率相关。我们研究了预处理的、化疗难治性转移性CRC(mCRC)患者的基线HTN和BB使用情况与总生存期(OS)和无进展生存期(PFS)的关系。我们还研究了基线HTN作为西妥昔单抗疗效预测指标的情况。
利用加拿大癌症试验组co.17研究[西妥昔单抗对比最佳支持治疗(BSC)]的数据,我们对572例患者的基线HTN及抗高血压药物(包括BBs)的使用情况进行了编码。采用卡方检验评估这些变量与基线特征之间的关联。采用Cox回归模型对HTN诊断和BB使用情况进行OS和PFS的单因素和多因素分析。
未发现基线HTN、BB使用及抗高血压药物使用情况对改善OS具有预后价值。基线HTN和BB使用情况并非西妥昔单抗获益的显著预测指标。
在化疗难治性mCRC中,基线HTN和BB使用情况均不是显著的预后因素。基线HTN和BB使用情况不能预测西妥昔单抗的获益情况。仍有必要进一步研究以确定基线HTN或BB使用情况对接受早期治疗的患者预后是否同样无显著影响。