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Background/Aims@#Vedolizumab is indicated for moderately-to-severely active ulcerative colitis (UC) and Crohn’s disease (CD). Because multiple factors may result in different pharmacokinetics and clinical efficacies, understanding determinants of vedolizumab clearance may enhance dose and treatment strategies. The aim was to characterize vedolizumab pharmacokinetics in Asian and non-Asian UC and CD patients. @*Methods@#Population pharmacokinetic analysis for repeated measures, using data from 5 studies, was conducted using nonlinear mixed-effects modeling. A Bayesian estimation approach in NONMEM 7.3 was utilized to leverage the predominantly sparse data available for this analysis with results from a prior population pharmacokinetic analysis of vedolizumab. @*Results@#Vedolizumab pharmacokinetics were described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half life of vedolizumab was 24.7 days for anti-vedolizumab antibody (AVA)-negative patients and 18.1 days for AVA-positive patients; linear clearance (CLL) was 0.165 L/day for AVA-negative patients and 0.246 L/day for AVA-positive patients; central (Vc) and peripheral compartment volumes of distribution were 3.16 L and 1.84 L, respectively. Interindividual variabilities (percent coefficient of variation) were 30.8% for CLL and 19% for Vc; interoccasion variability on CLL was 20.3%; residual variance was 17.8%. For albumin, body weight and AVA, only extreme values were identified as potentially clinically important predictors of CLL. The effect of race (Asianon-Asian) and diagnosis (UC/CD) on CLL was negligible and likely not of clinical importance. @*Conclusions@#Pharmacokinetic parameters were similar in Asian and non-Asian patients with moderately-to-severely active UC and CD. This analysis supports use of vedolizumab flat-fixed dosing in these patients. (Clinicaltrials.gov Identifiers: NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2). CCT 101; NCT02039505 and CCT-001; NCT02038920)
ABSTRACT
<b>Objectives:</b> The staging system of the International Union Against Cancer considers tumor deposits to be N1c in patients with no regional lymph node metastasis, but the significance of tumor deposits in patients with regional lymph node metastases is unclear. We investigated the effect of tumor deposits on overall survival in colorectal cancer patients with regional lymph node metastases.<br><b>Patients and Methods:</b> From 2000 to 2008, 551 patients underwent resections for colorectal cancer at our medical center. We excluded 87 patients who had distant metastases or had received neoadjuvant chemotherapy or radiotherapy from our study and statistically analyzed the remaining 464 patients.<br><b>Results:</b> Stepwise multivariate Cox proportional hazards analysis in patients with regional lymph node metastases showed only tumor deposits to be significant for overall survival (hazard ratio: 2.813; <i>P</i> = 0.0002). Recurrence was seen in 49.2% of patients with tumor deposits (30/61) compared with 14.4% of patients without them (58/403; <i>P</i> < 0.0001). Tumor deposits did not show the same effect on overall survival as lymph node metastases.<br><b>Conclusions:</b> Tumor deposits were significantly associated with poorer overall survival in colorectal cancer patients with regional lymph node metastases. The effect of tumor deposits on overall survival was between that of lymph node metastasis and distant metastasis.
ABSTRACT
<b>Objectives:</b> The staging system of the International Union Against Cancer considers tumor deposits to be N1c in patients with no regional lymph node metastasis, but the significance of tumor deposits in patients with regional lymph node metastases is unclear. We investigated the effect of tumor deposits on overall survival in colorectal cancer patients with regional lymph node metastases. <br><b>Patients and Methods:</b> From 2000 to 2008, 551 patients underwent resections for colorectal cancer at our medical center. We excluded 87 patients who had distant metastases or had received neoadjuvant chemotherapy or radiotherapy from our study andstatistically analyzed the remaining 464 patients. <br><b>Results:</b> Stepwise multivariate Cox proportional hazards analysis in patients with regional lymph node metastases showed only tumor deposits to be significant for overall survival (hazard ratio: 2.813; <i>P</i> = 0.0002). Recurrence was seen in 49.2% of patients with tumor deposits (30/61) compared with 14.4% of patients without them (58/403; <i>P</i> < 0.0001). Tumor deposits did not show the same effect on overall survival as lymph node metastases. <br><b>Conclusions:</b> Tumor deposits were significantly associated with poorer overall survival in colorectal cancer patients with regional lymph node metastases. The effect of tumor deposits on overall survival was between that of lymph node metastasis and distant metastasis.
ABSTRACT
In our hospital the palliative care committee has been held once a month since 2000. In 2007, a total of 1,583 cancer patients were admitted to our hospital orreceived medical care at home. The average length of hospital stay was 24 days. Of the total number of patients, 88.4% was informed that they had cancer. In the latter half of the year it increased to 92.6% because the palliative caretakers gave doctors accurate information on patients' psychology and social background. In October 2007 a questionnaire survey was conducted on those who visited our palliative care section on the occasion of the hospital festival. A total of 46 responded to our survey about the knowledge of palliative care, physician's precise explanation about the illness, image of opioids, desirable place of death and so on. Twenty-eight respondents (60.9%) did not know anything about palliative care. Forty-four (95.7%) wanted precise explanation of cancer. Thirty-four (73.9%) said they had had a night image of opioids after reading the panel. Twenty-eight (60.9%) responded they would rather stay at home until death. We should give healthy people more information about palliative care and opioids.