Background: Because the ELF regimen (etoposide, leucovorin and 5-FU) in advanced gastric cancer was recently advocated as an active, non-toxic schedule, and drug scheduling of etoposide proved to be important, we performed a pilot study using the original ELF regimen (A), followed by a phase II study of a modified ELF schedule (B) using oral etoposide.
Patients And Methods: Of the 40 patients entered in the consecutive trials 15 were treated according to the original ELF (A) and 25 according to the modified ELF regimen (B). The primary tumor was originally in the stomach in 22 and the oesophago-cardiac junction in 18. In 6 there was locally advanced and in 34 metastatic disease.
Results: Toxicity was mild in ELF (A): grade III leukopenia in 6/63 cycles. The ELF (B) caused slightly more myelosuppression: grade III leukopenia in 4/102 and grade IV in 2/102 cycles, resulting in septicaemia in two patients, and toxic death in one. No severe thrombocytopenia was seen. Hemorrhage (4 cases) was exclusively related to tumor progression. Response rates were 7% (0%-21%) and 28% (10%-46%) for ELF (A) and ELF (B), respectively. Subjective response, however, leading to a clinically significant decrease of dysphagia and pain, was seen in 53% and 56% of the patients.
Conclusions: The modified ELF regimen (B) can be applied safely on an out-patient basis, and shows moderate activity in advanced gastric cancer which leads to an improved quality of life.
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http://dx.doi.org/10.1093/oxfordjournals.annonc.a058705 | DOI Listing |
Heart
December 2024
Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Background: Bacteraemia and infective endocarditis (IE) are rare but severe complications of transcatheter aortic valve implantation (TAVI). Limited data exist on the incidence and microbiological profile of early bacteraemia in this population. This study aimed to evaluate the 6-month incidence of bacteraemia, IE and associated mortality following TAVI.
View Article and Find Full Text PDFJAC Antimicrob Resist
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Background: Sulbactam is an effective therapy for infections. Previous sulbactam pharmacokinetics/pharmacodynamics (PK/PD) analyses established exposure efficacy targets in plasma against pneumonia. Herein, we established sulbactam efficacy targets in epithelial lining fluid (ELF).
View Article and Find Full Text PDFJ Antimicrob Chemother
December 2024
Facultés de Médecine et de Pharmacie de Lyon, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Background And Objectives: Cefiderocol approved dosages are based on a prolonged infusion (PI) of 3 h that may not be adequate in all settings The objective of this study was to identify alternative cefiderocol dosage regimens based on short infusion (SI) or continuous infusion (CI).
Methods: We performed 1000-patient pharmacokinetic/pharmacodynamic (PK/PD) simulations based on a reference population model. Drug penetration into the epithelial lining fluid (ELF) was considered for pneumonia.
J Antimicrob Chemother
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Background: Murine pneumonia models play a fundamental role in the preclinical development of novel compounds seeking an indication for the treatment of pneumonia. It is vital that plasma exposures in these models are not used as a surrogate for exposure in pulmonary epithelial lining fluid (ELF). Herein, human-simulated regimens (HSRs) in both plasma and ELF of meropenem, cefiderocol and tobramycin are described in the standardized COMBINE murine neutropenic pneumonia model.
View Article and Find Full Text PDFJ Antimicrob Chemother
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA.
Background: Lack of uniformity in infection models complicates preclinical development. The COMBINE protocol has standardized the murine neutropenic pneumonia model. Herein we provide benchmark efficacy data of humanized exposures of tigecycline and levofloxacin in plasma and epithelial lining fluid (ELF) against a collection of Klebsiella pneumoniae and Pseudomonas aeruginosa.
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