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1.
Ann Oncol ; 30(8): 1304-1310, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31228203

ABSTRACT

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). METHODS: Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. RESULTS: In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3-126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61-1.55); P = 0.647]. Eighty DFS events (3M N = 41; 6M N = 39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68-1.63, P = 0.829). For stage III patients, 314 DFS events (3M N = 161 and 6M N = 153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81-1.42, P = 0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54-2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59-1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74-1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70-1.44). CONCLUSIONS: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01308086.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Capecitabine/administration & dosage , Colonic Neoplasms/therapy , Duration of Therapy , Oxaloacetates/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/adverse effects , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/methods , Colectomy , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Greece/epidemiology , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaloacetates/adverse effects , Patient Selection , Survival Rate , Time Factors , Young Adult
2.
Cancer Chemother Pharmacol ; 78(2): 369-76, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27335027

ABSTRACT

INTRODUCTION: The addition of bevacizumab to the first-line chemotherapy of advanced non-small cell lung cancer (NSCLC) of non-squamous histology has been shown to improve survival. A multicenter, single-arm, phase IV study was conducted in order to evaluate the efficacy and toxicity of frontline bevacizumab-based chemotherapy regimens in real life. METHODS: Patients with previously untreated recurrent or metastatic non-squamous, NSCLC, with no contraindications for bevacizumab, were enrolled. Bevacizumab (15 mg/kg every 3 weeks) was administered in combination with both platinum- and non-platinum-based chemotherapy doublets or with single-agent chemotherapy plus bevacizumab. Treatment with bevacizumab was continued until disease progression. The primary end point of the study was the safety profile of bevacizumab regimens, whereas the secondary end points included overall survival, progression-free survival, and overall response rate. RESULTS: From February 2010 to April 2014, a total of 314 patients were enrolled in the study; the median age was 63, 74.8 % were men, 95.9 % had a performance status of 0-1, 90.4 % had metastatic disease, and 94.3 % had adenocarcinoma. Grade ≥3 neutropenia occurred in 11.5 % of the patients, 1.3 % experienced febrile neutropenia, 2.6 % grade ≥3 thrombocytopenia, 2.8 % thromboembolism, and 1.6 % severe bleeding. Treatment discontinuation occurred in 7.0 % of patients because of adverse events. There were three toxic deaths. Median progression-free survival was 7.7 months, and median overall survival was 17.6 months. CONCLUSION: The combination of bevacizumab with chemotherapy in the first-line setting of NSCLC is safe and active when used in appropriately selected patients. CLINICALTRIALS. GOV IDENTIFIER: NCT01934465.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Patient Selection , Survival Rate , Treatment Outcome
3.
Chemotherapy ; 44(4): 260-4, 1998.
Article in English | MEDLINE | ID: mdl-9681202

ABSTRACT

The in vitro activity of loracarbef was evaluated against Escherichia coli strains producing TEM extended-spectrum beta-lactamases (ESBLs). The MICs of loracarbef were lower than those of cefaclor and cephalothin. The antibiotic was active (MICs < or = 2 mg/l) against strains producing TEM-6, TEM-8, TEM-10, TEM-16, TEM-26 and TEM-28 beta-lactamases. The MICs for TEM-3-, TEM-5- and TEM-24-producing strains were higher (> or = 16 mg/l). Hydrolysis studies indicated that the latter beta-lactamases inactivated loracarbef more efficiently than the remaining TEM-type ESBLs examined.


Subject(s)
Cephalosporins/pharmacology , Escherichia coli/drug effects , beta-Lactamases/metabolism , Cephalosporins/metabolism , Drug Stability , Escherichia coli/enzymology , Hydrolysis , Microbial Sensitivity Tests , Plasmids/genetics , beta-Lactam Resistance , beta-Lactamases/chemistry
4.
J Clin Microbiol ; 36(1): 266-8, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9431962

ABSTRACT

The sporadic emergence of Klebsiella pneumoniae strains resistant to cefepime and cefpirome was observed in Greek hospitals during 1996. Examination of six epidemiologically distinct strains and clones selected in vitro provided indications that resistance is due to the cooperation of decreased outer membrane permeability and hydrolysis of the cephalosporins by SHV-5 beta-lactamase, which was produced in large amounts.


Subject(s)
Cephalosporins/pharmacology , Klebsiella pneumoniae/drug effects , Cefepime , Drug Resistance, Microbial , Humans , Microbial Sensitivity Tests , Cefpirome
5.
Antimicrob Agents Chemother ; 41(4): 838-40, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9087500

ABSTRACT

An inhibitor-resistant beta-lactamase (SHV-10), derived from an SHV-5 variant (SHV-9), was found in an Escherichia coli clinical isolate. In SHV-10, Ser-130 was replaced by Gly. The enzyme partially retained its ability to hydrolyze penicillins, but its activity against cephalosporins was drastically reduced. A Ser-130-->Gly mutant of the prototype SHV-5, obtained by site-directed mutagenesis, had properties similar to those of SHV-10.


Subject(s)
Escherichia coli/enzymology , beta-Lactamase Inhibitors , Anti-Bacterial Agents/metabolism , Drug Resistance, Microbial , Escherichia coli Infections/microbiology , Humans , beta-Lactamases/genetics , beta-Lactams
6.
Antimicrob Agents Chemother ; 41(2): 475-7, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9021212

ABSTRACT

The inhibitory activity of the penicillanic acid sulfone Ro 48-1220 against group 1, 2b, and 2be beta-lactamases was evaluated. Ro 48-1220 inhibited TEM and SHV as effectively as clavulanate and tazobactam. It also inhibited group 1 beta-lactamases at lower concentrations than tazobactam. Ro 48-1220, at a concentration of 4 micrograms/ml, protected ceftriaxone and ceftazidime against strains producing group 1 and 2be beta-lactamases.


Subject(s)
Bacteria/drug effects , Penicillanic Acid/analogs & derivatives , beta-Lactamase Inhibitors , Bacteria/enzymology , Drug Resistance, Microbial , Penicillanic Acid/pharmacology , beta-Lactamases
7.
Chemotherapy ; 42(5): 324-8, 1996.
Article in English | MEDLINE | ID: mdl-8874970

ABSTRACT

The in vitro activity of cefetamet against Escherichia coli, Klebsiella pneumoniae and Serratia marcescens strains expressing an SHV-5-type beta-lactamase was evaluated. Most of the examined strains were susceptible to the antibiotic. Cefetamet was found to be considerably more active than ceftazidime and aztreonam. Its activity was comparable to that of cefotaxime. Cefetamet MIC values were related to the quantity of the enzyme expressed. The SHV-5-type enzyme hydrolysed cefetamet with an efficiency (Vmax/Km) similar to that of ceftazidime.


Subject(s)
Ceftizoxime/analogs & derivatives , Cephalosporins/pharmacology , Enterobacteriaceae/drug effects , beta-Lactamases/metabolism , Ceftizoxime/pharmacology , Enterobacteriaceae/enzymology , Escherichia coli/drug effects , Escherichia coli/enzymology , Isoelectric Focusing , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Microbial Sensitivity Tests , Serratia marcescens/drug effects , Serratia marcescens/enzymology , beta-Lactam Resistance
8.
Antimicrob Agents Chemother ; 40(7): 1736-40, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8807075

ABSTRACT

Cefoxitin resistance in Klebsiella pneumoniae from Escherichia coli strains isolated in Greek hospitals was found to be due to the acquisition of similar plasmids coding for group 1 beta-lactamases. The plasmids were not self-transferable but were mobilized by conjugative plasmids. These elements have also been spread to Enterobacter aerogenes. The most common enzyme was a Citrobacter freundii-derived cephalosporinase (LAT-2) which differed from LAT-1 by three amino acids.


Subject(s)
Cefoxitin/pharmacology , Cephamycins/pharmacology , Cross Infection/microbiology , Enterobacteriaceae/drug effects , Enterobacteriaceae/genetics , Penicillinase/genetics , Amino Acid Sequence , Base Sequence , Citrobacter freundii/drug effects , Citrobacter freundii/enzymology , Citrobacter freundii/genetics , Conjugation, Genetic , Drug Resistance, Microbial , Enterobacter/drug effects , Enterobacter/enzymology , Enterobacter/genetics , Enterobacteriaceae/enzymology , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli/genetics , Greece , Microbial Sensitivity Tests , Molecular Sequence Data , Plasmids
9.
FEMS Microbiol Lett ; 139(2-3): 229-34, 1996 Jun 01.
Article in English | MEDLINE | ID: mdl-8674992

ABSTRACT

An SHV type beta-lactamase frequently found in enterobacteria isolated in Greek hospitals was analyzed. The enzyme (SHV-5a) conferred resistance to ceftazidime and aztreonam. The DNA sequence of the structural gene was determined. The deduced amino acid sequence showed that positions 70-73 were occupied by the active site tetrad Ser-Thr-Phe-Lys. As in SHV-5, Ser-238 and Lys-240 were present. However, one deletion (Gly-54) and three substitutions (Arg-140 for Ala, Asn-192 for Lys and Val-193 for Leu) differentiate SHV-5a beta-lactamase from SHV-5. Asn-192 and Val-193 have been reported to date only in the R974 plasmid-mediate SHV-1 beta-lactamase. Hydrolysis studies with SHV-5a and SHV-5 showed that the enzymes behaved similarly. Additional evidence that they are functionally indistinguishable was provided by the similar MICs of beta-lactams when the enzymes were expressed under isogenic conditions. The sequence differences, however, indicate that they are derived from different ancestors.


Subject(s)
Enterobacteriaceae/enzymology , beta-Lactamases/genetics , Amino Acid Sequence , Base Sequence , DNA, Bacterial/analysis , Enterobacteriaceae/genetics , Escherichia coli/enzymology , Escherichia coli/genetics , Genetic Variation , Isoelectric Focusing , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/genetics , Molecular Sequence Data , Plasmids , Serratia marcescens/enzymology , Serratia marcescens/genetics
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