3 research outputs found
Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer - A randomized phase III study conducted by the Hellenic Cooperative Oncology Group
Background: It has been shown in randomized studies that adjuvant
treatment with the combination of fluorouracil (FU) and levamisole
reduced the risk of recurrence and deaths of patients with stage III
colon cancer. Pharmacological studies of FU led to its use in
combination with a number of modulating agents including interferon-a
and leucovorin (LV) that appear to enhance its activity in vitro.
Furthermore, a meta-analysis suggested that the combination of FU with
LV increased the response rate as compared to FU monotherapy in patients
with advanced colorectal cancer. Purpose: To evaluate the impact of
adjuvant treatment with the combination of FU and LV with or without
interferon alfa-2a (IFN) on disease-free survival (DFS) and overall
survival (OS) for patients with stage II or III colon cancer. Patients
and Methods: From August 1989 to July 1997, 280 patients with stage II
and III colon cancer entered the study and were randomly assigned to
receive either the combination of FU (600 mg/m(2)/week x 6, followed by
a 2-week rest) and LV (500 mg/m(2)/week x 6 as a 2-hour infusion,
followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the
same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a
week) for 1 year (group B, 141 patients). Results: A total of 109
patients (78.9%) of group A and 119 (84.4%) of group B complated four
cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9%
of group B received greater than or equal to 80% of the planned dose of
FU. One patient (group A) was found to be ineligible and was not
included in the analysis. The median relative dose intensity of FU in
the two groups was 0.90 and 0.85, respectively. As of August 1998, after
a median follow up of 4 years, there was no significant difference in
either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS
(group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of
disease, number of infiltrated nodes, tumor grade and presence of
regional implants were identified as significant prognostic factors for
OS. Grade 3-4 toxicities, mainly diarrhea, were observed in 26.1% of
patients of group A and in 24.8% of group B, There were no
treatment-related deaths. Conclusions: The addition of IFN to the
combination of FU with LV postoperatively does not improve DFS and OS of
patients with stage II or III colon cancer. Copyright (C) 2000 S. Karger
AG, Basel
Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
OBJECTIVE:
Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD.
DESIGN:
This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates.
SETTING AND PARTICIPANTS:
448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries.
RESULTS:
Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (\u3b2 = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates.
CONCLUSIONS AND IMPLICATIONS:
This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD