Survival Benefit Demonstrated with FOLFIRINOX in Select Patients with Metastatic Pancreatic Cancer
Clinical question: How does FOLFIRINOX compare to gemcitabine as first-line treatment of metastatic pancreatic cancer?
Background: Single-agent gemcitabine is the standard first-line treatment for metastatic pancreatic cancer. Preclinical studies followed by Phase 1 and Phase 2 studies have demonstrated response to the oxaliplatin, irinotecan, leucovorin, and fluorouracil regimen (FOLFIRINOX).
Study design: Multicenter, randomized, controlled Phase 2-3 trial.
Setting: Fifteen centers in France during Phase 2, which then expanded to 48 centers for Phase 3.
Synopsis: Three hundred forty-two patients with good performance status (ECOG 0 or 1) and age <76 were randomized to receive FOLFIRINOX or gemcitabine. Median survival in the FOLFIRINOX group was significantly increased, at 11.1 months, compared with 6.8 months in the gemcitabine group (HR 0.57, CI 95%, 0.45-0.73, P<000.1).
Median progression-free survival, objective response rate, and quality of life score at six months were significantly increased in the FOLFIRINOX group. Significantly more grade 3 or grade 4 toxicity was reported in the FOLFIRINOX group.
Patients with elevated bilirubin were excluded due to increased risk of irinotecan-induced toxicity, resulting in only 38% of study patients with carcinoma of the pancreatic head and low proportion of enrolled patients (14.3%) with biliary stents.
Bottom line: FOLFIRONOX was associated with a significant survival advantage compared with single-agent gemcitabine in carefully selected patients with advanced pancreatic cancer, although it was associated with increased toxicity.
Citation: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825.
MRSA Bundle Implementation at VA Hospitals Reduced Healthcare-Associated MRSA Infections
Clinical question: Can nationwide implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, influence healthcare-associated MRSA infection rates?
Background: MRSA is a common cause of nosocomial infection. A pilot project at a single Veterans Affairs (VA) hospital utilized a “MRSA bundle” developed from published guidelines, which resulted in decreased healthcare-associated MRSA infections. In October 2007, the MRSA bundle was implemented throughout VA hospitals nationwide.
Study design: Quality-improvement (QI) observational initiative.
Setting: One hundred fifty-eight acute-care VA hospitals in the U.S.
Synopsis: From October 2007 to June 2010, there were 1,934,598 admissions, transfers, or discharges, and 8,318,675 patient-days. Of this study group, 96% of patients were screened at admission and 93% were screened at transfer or discharge. MRSA colonization or infection at the time of admission was 13.6%. Rates of healthcare-associated MRSA infection declined 45% in the non-ICU setting (0.47 to 0.26 per 1,000 patient-days, P<0.001) and 62% in the ICU setting (1.64 to 0.62 per 1,000 patient days, P<0.001).
It is unclear how much each individual component of the MRSA bundle impacted the declining MRSA infection rate.
Bottom line: Implementation of a “MRSA bundle,” including universal surveillance, contact isolation, hand hygiene, and institutional culture change, decreased the healthcare-associated MRSA infection rate in a large hospital system.
Citation: Jain R, Kralovi S, Evans M, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-1430.
New Left Bundle Branch Block Does Not Predict MI
Clinical question: How does the chronicity of left bundle branch block (LBBB) impact diagnosis and outcome in patients undergoing evaluation for acute myocardial infarction (MI)?
Background: ACA/AHA guidelines recommend that patients with new or presumed new LBBB undergo early reperfusion therapy. However, previous studies have shown that a minority of patients with new LBBB are diagnosed with MI.
Study design: Prospective cohort study.