In vitro evaluation of cefepime and other broad-spectrum β-lactams in 22 medical centers in Japan: a phase II trial comparing two annual organism samples

1999 ◽  
Vol 35 (4) ◽  
pp. 307-315 ◽  
Author(s):  
M.Todd Lewis ◽  
Keizo Yamaguchi ◽  
Douglas J. Biedenbach ◽  
Ronald N. Jones
Keyword(s):  
Phase Ii ◽  
Broad Spectrum ◽  
Phase Ii Trial ◽  
In Vitro Evaluation ◽  
Medical Centers

In vitro evaluation of cefepime and other broad-spectrum β-lactams in eight medical centers in Thailand

1999 ◽  
Vol 35 (4) ◽  
pp. 325-331 ◽  
Author(s):  
Douglas J. Biedenbach ◽  
David M. Johnson ◽  
Ronald N. Jones
Keyword(s):  
Broad Spectrum ◽  
In Vitro Evaluation ◽  
Medical Centers

In vitro evaluation of cefepime and other broad-spectrum β-lactams in Taiwan medical centers

1999 ◽  
Vol 35 (4) ◽  
pp. 299-305 ◽  
Author(s):  
Douglas J. Biedenbach ◽  
David M. Johnson ◽  
Ronald N. Jones
Keyword(s):  
Broad Spectrum ◽  
In Vitro Evaluation ◽  
Medical Centers

An in vitro evaluation of clavulanic acid, a potent, broad-spectrum β-lactamase inhibitor

1979 ◽  
Vol 5 (5) ◽  
pp. 539-547 ◽  
Author(s):  
David Greenwood ◽  
Francis O'Grady ◽  
Paul Baker
Keyword(s):  
Clavulanic Acid ◽  
Broad Spectrum ◽  
In Vitro Evaluation ◽  
Lactamase Inhibitor

Defining molecular determinants of sensitivity to EGFR inhibition in urothelial carinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 268-268
Author(s):  
W. Y. Kim ◽  
T. Hadzic ◽  
S. A. Heathcote ◽  
D. T. Gammons ◽  
K. Rathmell ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Expression Profiles ◽  
Clinical Activity ◽  
Egfr Inhibition ◽  
T24 Cells ◽  
Molecular Determinants ◽  
Muscle Invasive

268 Background: Activation of EGFR in cancer patients has been shown to correlate with tumor proliferation, angiogenesis, and metastasis. EGFR inhibition has been shown to be clinically beneficial in several solid tumors and appears to be a tractable therapeutic target. EGFR is over-expressed in bladder cancer and a phase II trial of neoadjuvant erlotinib in patients with muscle invasive bladder cancer suggests possible clinical activity. We therefore hypothesized that we could define molecular correlates to predict response to EGFR inhibition. Methods: Correlative tumor samples derived from a phase II trial of neoadjuvant erlotinib in muscle invasive urothelial carcinoma of the bladder were analyzed to define molecular determinants of response to EGFR inhibition. The effect of silencing a candidate molecular predictor of resistance to EGFR inhibition, HRAS, was assessed by changes in the IC50 of T24 cells (harbor mutant HRAS) expressing short hairpin RNAs to HRAS or a control shRNA. Results: Analysis of the gene expression profiles of TURB-T (pretreatment) samples show that tumors from non-pT0 patients had significantly elevated levels of HRAS relative to tumors from pT0 patients. Furthermore, knock-down of HRAS in T24 cells enhanced the sensitivity of these cells to erlotinib. Conclusions: Elevated HRAS expression is correlated with a lack of response to erlotinib in vivo and silencing of HRAS in T24 cells results in enhanced sensitivity to erlotinib in vitro. Further molecular analyses are ongoing. No significant financial relationships to disclose.

Bendamustine in Combination with Rituximab (BR) for Patients with Relapsed Chronic Lymphocytic Leukemia (CLL): A Multicentre Phase II Trial of the German CLL Study Group (GCLLSG).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3106-3106 ◽  
Author(s):  
Kirsten Fischer ◽  
Stephan Stilgenbauer ◽  
Carmen D. Schweighofer ◽  
Jasmin Renschler ◽  
Raymonde Busch ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Residual Disease ◽  
Ex Vivo ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Entire Study ◽  
Mutational Status ◽  
Grade 3

Abstract Introduction: Bendamustine has shown considerable activity in monotherapy for solid and lymphoid malignancies including CLL and has been used for more than 30 years in anti-cancer treatment. In vitro and ex vivo studies have demonstrated synergistic pro-apoptotic effects of bendamustine and the CD20 antibody rituximab (BR) in primary B-CLL cells. Encouraging clinical results have been obtained using BR combination treatment in relapsed/refractory NHL or mantle cell lymphoma. The present phase II trial represents the first study assessing efficacy and toxicity of bendamustine in combination with rituximab in pts with relapsed/refractory B-CLL. Patients and Methods: Between March 2006 and June 2007 81 pts with relapsed/refractory B-CLL and a median number of 2 pretreatments were enrolled into this trial. Bendamustine was given at a dose of 70 mg/m2 on day 1 and 2, combined with 375mg/m2 rituximab for the first cycle and 500 mg/m2 for the second and subsequent cycles. BR treatment was administered every 28 days up to 6 courses. Blood samples were taken for molecular cytogenetics by fluorescence in situ hybridization (FISH), analysis of the IgVH mutational status and expression of ZAP70/CD38. Assessment of minimal residual disease (MRD) was evaluated in peripheral blood and bone marrow by 4-colour flow cytometry. Results: So far data of 31 pts (median age 66 years) with a total of 126 treatment cycles are available for analysis. There was notable toxicity with 48 reported CTC grade 3/4 adverse events, particularly myelosuppression and infections: grade 3/4 anemia occurred in 6.3.%, leukopenia/neutropenia in 10.8% and thrombocytopenia in 11.9% of all courses. 6 episodes of CTC grade 3/4 infections were documented: 1 sinusitis maxillaris, 1 FUO and 1 abscess, all of them being reversible after antibiotics. However, 3 pts died due to severe infections including 2 fatal pneumonias and 1 urosepsis. One pt died due to myocardial infarction. Regarding efficacy, 23 pts were evaluable for response: The overall response rate (ORR) was 65.2% with a CR rate of 13.0% (3 pts) and a PR rate of 52.2% (12 pts). No molecular remission was observed by 4-colour cytometry. Stable disease (SD) was achieved in 26.1% (6 pts) whereas 2 pts had progressive CLL (PD, 8.7%). Responses were observed in the majority of pts with genomic aberrations 11q deletion (ORR: 4/5) and trisomy 12 (ORR: 2/3), while none of the pts with 17p deletion (ORR: 0/4) was responsive (P=0.006). Conclusion: Bendamustine plus rituximab is an effective regimen in refractory/relapsed B-CLL. Major treatment toxicities were myelosuppression and infections. Updated data with respect to toxicity and efficacy based on the entire study population will be available for the Meeting.

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