Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.

BACKGROUND: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). METHODS: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. RESULTS: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. CONCLUSION: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.

Evaluation of Postnatal Sedation in Full-Term Infants.

Prolonged sedation in infants leads to a high incidence of physical dependence. We inquired: (1) "How long does it take to develop physical dependence to sedation in previously naïve full-term infants without known history of neurologic impairment?" and (2) "What is the relationship between length of sedation to length of weaning and hospital stay?". The retrospective study included full-term patients over a period of one year that were <1 year of age and received opioids and benzodiazepines >72 hours. Quantification of fentanyl, morphine, and midazolam were compared among three time periods: <5 days, 5-30 days, and >30 days using t-test or one-way analysis of variance. Identified full-term infants were categorized into surgical (14/44) or medical (10/44) groups, while those with neurological involvement (20/44) were excluded. Physical dependence in full-term infants occurred following sedation ≥5 days. Infants with surgical disease received escalating doses of morphine and midazolam when administered >30 days. A positive association between length of sedation and weaning period was found for both respiratory (p < 0.01) and surgical disease (p = 0.012) groups, while length of sedation is related to hospital stay for the respiratory (p < 0.01) but not the surgical disease group (p = 0.1). Future pharmacological directions should lead to standardized sedation protocols and evaluate patient neurocognitive outcomes.