10 research outputs found
Randomized phase II trial of FOLFIRI-panitumumab compared with FOLFIRI alone in patients with RAS wild-type circulating tumor DNA metastatic colorectal cancer beyond progression to first-line FOLFOX-panitumumab : the BEYOND study (GEMCAD 17-01)
Altres ajuts: Fundació la Marató de TV3 (201330.10); Fundacion Olga Torres (Modalitat A. 2019/2020); Spanish Association Against Cancer (AECC, PROYE19040POST_001).Purpose: Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB). Methods: In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38). Results: Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B. Conclusions: The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation
Tuning Lewis Acidity of Metal–Organic Frameworks via Perfluorination of Bridging Ligands: Spectroscopic, Theoretical, and Catalytic Studies
The Lewis acidity of metal–organic
frameworks (MOFs) has
attracted much research interest in recent years. We report here the
development of two quantitative methods for determining the Lewis
acidity of MOFsbased on electron paramagnetic resonance (EPR)
spectroscopy of MOF-bound superoxide (O<sub>2</sub><sup>•–</sup>) and fluorescence spectroscopy of MOF-bound <i>N</i>-methylacridone
(NMA)and a simple strategy that significantly enhances MOF
Lewis acidity through ligand perfluorination. Two new perfluorinated
MOFs, Zr<sub>6</sub>-fBDC and Zr<sub>6</sub>-fBPDC, where H<sub>2</sub>fBDC is 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylic acid and H<sub>2</sub>fBPDC is 2,2′,3,3′,5,5′,6,6′-octafluoro-4,4′-biphenyldicarboxylic
acid, were shown to be significantly more Lewis acidic than nonsubstituted
UiO-66 and UiO-67 as well as the nitrated MOFs Zr<sub>6</sub>-BDC-NO<sub>2</sub> and Zr<sub>6</sub>-BPDC-(NO<sub>2</sub>)<sub>2</sub>. Zr<sub>6</sub>-fBDC was shown to be a highly active single-site solid Lewis
acid catalyst for Diels–Alder and arene C–H iodination
reactions. Thus, this work establishes the important role of ligand
perfluorination in enhancing MOF Lewis acidity and the potential of
designing highly Lewis acidic MOFs for fine chemical synthesis
Tuning Lewis Acidity of Metal–Organic Frameworks via Perfluorination of Bridging Ligands: Spectroscopic, Theoretical, and Catalytic Studies
The Lewis acidity of metal–organic
frameworks (MOFs) has
attracted much research interest in recent years. We report here the
development of two quantitative methods for determining the Lewis
acidity of MOFsbased on electron paramagnetic resonance (EPR)
spectroscopy of MOF-bound superoxide (O<sub>2</sub><sup>•–</sup>) and fluorescence spectroscopy of MOF-bound <i>N</i>-methylacridone
(NMA)and a simple strategy that significantly enhances MOF
Lewis acidity through ligand perfluorination. Two new perfluorinated
MOFs, Zr<sub>6</sub>-fBDC and Zr<sub>6</sub>-fBPDC, where H<sub>2</sub>fBDC is 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylic acid and H<sub>2</sub>fBPDC is 2,2′,3,3′,5,5′,6,6′-octafluoro-4,4′-biphenyldicarboxylic
acid, were shown to be significantly more Lewis acidic than nonsubstituted
UiO-66 and UiO-67 as well as the nitrated MOFs Zr<sub>6</sub>-BDC-NO<sub>2</sub> and Zr<sub>6</sub>-BPDC-(NO<sub>2</sub>)<sub>2</sub>. Zr<sub>6</sub>-fBDC was shown to be a highly active single-site solid Lewis
acid catalyst for Diels–Alder and arene C–H iodination
reactions. Thus, this work establishes the important role of ligand
perfluorination in enhancing MOF Lewis acidity and the potential of
designing highly Lewis acidic MOFs for fine chemical synthesis