Background 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.Methods 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.Results 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.Conclusions 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.
256 Background: Adrenergic receptor stimulation is involved in development of hypertension (HTN), and is implicated in progression and dissemination of metastases in tumour types such as colon cancer (CRC). Adrenergic antagonists, such as beta-blockers (BB), demonstrate inhibition of invasion and migration in CRC cell lines and have been associated with decreased mortality in advanced CRC. We examined the association of baseline HTN (BHTN) and use of BB on overall (OS) or progression-free survival (PFS) of pts with pre-treated, chemotherapy refractory, metastatic CRC (mCRC). We also examined BHTN and BB use as predictors of Cetuximab (CET) efficacy. Methods: Using data from NCIC CO.17 (CET vs. BSC), we coded BHTN and use of anti-HTN meds (Rx), including BB, for 572 pts. Chi-square test assessed association between these variables and baseline characteristics. Univariate and multivariate analyses of OS and PFS by BHTN diagnosis and BB use were performed using Cox regression models. Results: Pts with BHTN (149/572) and those using BB (60/572) were older, had diminished performance status, and higher creatinine levels. BHTN, BB use and anti-HTN Rx were not prognostic for OS and PFS, though a trend was noted between BB use and improved PFS (HR 1.38 [0.97- 1.96], p= 0.077). BHTN and BB use were not significant predictors of CET benefit. However, pts with BHTN tended to have a stronger treatment effect in PFS from CET (interaction p = 0.074). Conclusions: In chemo-refractory mCRC, BHTN and BB use are not significant prognostic factors. BHTN and BB use are also not predictive of CET benefit, though pts with baseline HTN may benefit from a stronger treatment effect with CET. Patients with chemo-refractory mCRC may be biologically selected and the impact of BB use in earlier lines may therefore still warrant investigation. [Table: see text]
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