Summary
Background
Taxanes are the current first‐line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or ...comorbidity. However, no effective second‐line therapy for such patients has been established.
Methods
We designed a single‐arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m−2 on days 1 and 8 in a 21‐day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression‐free survival (PFS) and toxicity assessment.
Results
We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference.
Conclusions
ERB showed a promising RR and is a potential candidate for second‐line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients.
What is already known about this topic?
Taxanes are the current first‐line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity.
No effective therapy for taxane‐resistant CAS has been established thus far.
Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes.
What does this study add?
In our single‐arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression‐free survival were 8·6 and 3·0 months, respectively.
Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively.
Although 16 grade 3/4 severe adverse events occurred, all patients recovered.
Eribulin showed a promising response rate and is a potential candidate for second‐line treatment in CAS after taxane treatment.
Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797–798.
What is already known about this topic?
Taxanes are the current first‐line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity.
No effective therapy for taxane‐resistant CAS has been established thus far.
Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes.
What does this study add?
In our single‐arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression‐free survival were 8·6 and 3·0 months, respectively.
Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively.
Although 16 grade 3/4 severe adverse events occurred, all patients recovered.
Eribulin showed a promising response rate and is a potential candidate for second‐line treatment in CAS after taxane treatment.
Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797–798.
Solutions of Nafion® with an ion exchange capacity (IEC) of 0.91 meq g
−1
, which are on the verge of the formation of SO
3
H nanoclusters, were spin coated on silicon (Si), glassy carbon (GC) and ...platinum/silicon (Pt/Si) substrates to form films of up to 256 nm thickness. Nanostructure of the films was studied using Doppler broadening of annihilation radiation (DBAR), positron annihilation lifetime (PAL), X-ray photoelectron spectroscopy (XPS), an atomic force microscope (AFM) and contact angle measurements. Contact angles as low as 10 degrees indicate that the surface of dry ultrathin Nafion® films on Si is highly hydrophilic. XPS data of 10 nm thick, ultrathin film on Si show that oxygen concentration is enhanced and the SO
3
H group concentration, in other words, IEC on the surface is much higher than other films. The
S
parameter measured by DBAR of an ultrathin Nafion® film on Si is much higher than that of the films on the other substrates. We consider that a large number of hydrophilic, reversed micelle like SO
3
H groups are on the surface of the ultrathin Nafion® film on Si but not on the surface of other films. Positrons implanted into the film are trapped by the SO
3
H clusters, annihilating with the electrons of oxygen and exhibit the high
S
parameter. The SO
3
H concentration on the surface of thin Nafion® films on GC and Pt/Si substrates may not be so high as the threshold for the formation of a large number of SO
3
H clusters. Positrons implanted into the films annihilate mostly with fluorine atoms, resulting in a low
S
parameter. The film-substrate interaction plays an essential role in nanostructuring of Nafion® thin films, which may also be the case for Nafion® on the catalysts of polymer electrolyte fuel cells.
Schematic drawing of the adsorption model of ultrathin Nafion® films on different substrates.
The mechanism of gas permeation in Nafion membranes for polymer electrolyte fuel cells has been investigated from the viewpoint of free volume. Three different samples, a membrane with ionic exchange ...capacity (IEC)=0.92meq/g, and recast samples with IEC=0.92 and 1.00meq/g were used after drying. Free volume was quantified using the positron annihilation lifetime (PAL) technique and gas permeabilities were measured for O2 and H2 as functions of temperature and relative humidity. Good linear correlations between the logarithm of the permeabilities at different temperatures and reciprocal free volume indicate that gas permeation in dry Nafion is governed by the free volume. Nevertheless permeabilities are much smaller than the corresponding flexible chain polymer with a similar free volume size due to stiff chains of the perfluoroethylene backbone. In highly hydrated Nafion above 60% relative humidity, where the O2 permeability varies oppositely to the free volume, gas permeation proved to be controlled by the gradual increase in overall flexibility of the Nafion–water system.
Variations of the free volume, O2 permeability, and structure of the Nafion membrane upon ion exchange of H+ with Na+ and K+ were studied. The free volume was quantified using the positron ...annihilation lifetime (PAL) technique, whereas the polymer structure was characterized by dynamic mechanical analysis (DMA), nanoindentation, and wide-angle X-ray diffraction (WAXD). It was found that the ion exchange significantly expands the free volume and at the same time decreases the O2 permeability. This is opposed to the simple free volume model in which the structure with less open volume is more amenable to lower permeability. Comparison of experimental data collected by different techniques revealed that not only the free volume but also the polymer stiffness plays an essential role in O2 permeation.
We measured the yield of positronium (Ps) in sulfonated aromatic proton conducting membranes for the polymer electrolyte fuel cell (PEFC) with and without −SO2− in their chemical structures by ...positron annihilation lifetime spectroscopy (PALS). It was observed that Ps formation is almost totally inhibited in the polymers without −SO2− such as sulfonated poly(ether ether ketone) (SPEEK). On the other hand Ps favorably forms in those with −SO2− as sulfonated polyether sulfone (SPES), which is due to the anti-inhibition effect of −SO2−. The high probability of Ps formation in these polymers enables the study of the free volume and the mechanism of gas permeation by PALS.
We investigated the 1H time-dependent self-diffusion coefficients, D eff, in perfluorinated membrane with low and high water contents (6% and 24%) at the temperature range from 233 to 323 K. The ...D(Δeff) was measured as a function of the diffusion time, Δeff, from 1 to 100 ms by field gradient NMR techniques. The oscillating gradient spin-echo sequence (OGSE) and the bipolar pulse longitudinal eddy current delay sequence (BPPLED) were employed to examine the D(Δeff) of the short and long Δeff. The results showed that the 1H self-diffusion coefficients were dependent on Δeff less than 2 ms due to restricted geometry and were constant beyond 3 ms. The tortuosity, α, and surface-to-volume ratio of pore, S/V, for proton diffusion were estimated as geometrical parameters at each temperature. The values of S/V revealed the existence of micron-scale restricted structure compared with well-known nanometer-sized domain in perfluorinated membrane. Activation energy, E a, of diffusion was also evaluated from the temperature dependence of diffusion at temperature above 263 K. The E a in the membrane and in the bulk water were almost the same at the temperature range above 263 K while it had some difference at lower temperature.
Free volume, O
2 permeability, and uniaxial compression storage modulus of biphenol-based sulfonated poly(arylene ether sulfone) (BPSH) with an ion exchange capacity (IEC) of 1.60
mequiv./g were ...studied as a function of relative humidity at room temperature. The free volume hole size was quantified using the positron annihilation lifetime (PAL) technique, whereas the uniaxial compression storage modulus was measured by dynamic nanoindentation. Favorable formation of positronium (Ps) due to the anti-inhibition effect of –SO
2– allowed for the application of the PAL technique to the study of free volume in BPSH. It was found that as the polymer is hydrated the free volume hole size (
V
FV,Ps) and O
2 permeability (
P
O
2
) first decrease and then increase. A semi-logarithmic plot of
P
O
2
versus 1/
V
FV,Ps for BPSH at different relative humidities showed a good correlation similar to that for different polymers such as polystyrene and polycarbonate in the dry state. Tendency of
P
O
2
deviating from the correlation in highly hydrated BPSH suggests an effect of polymer softening on O
2 permeation in addition to the dominant effect of the free volume.
The mechanism of gas permeation in per-fluorinated sulfonic acid PTFE copolymer Fumapem® membranes for polymer electrolyte fuel cells has been investigated from the viewpoint of free volume. Three ...different samples, Fumapem® F-950, F-1050 and F-14100 membranes with ion exchange capacity (IEC) = 1.05, 0.95 and 0.71 meq g, respectively were used after drying. Free volume was quantified using the positron annihilation lifetime (PAL) technique and gas permeabilities were measured for O2 and H2 as function of temperature. Good linear correlation between the logarithm of the permeabilities at different temperatures and reciprocal free volume indicate that gas permeation in dry Fumapem® is governed by the free volume. Nevertheless permeabilities are much smaller than the corresponding flexible chain polymer with a similar free volume size due to stiff chains of the perfluoroethylene backbone.
Solid‐state films of chiral polysilanes undergo an optical inversion (see Figure) above a helix–helix transition temperature, determined by the polymer molecular weight and by the thermal processing. ...These films could be used for re‐writable or write‐once, read‐many data storage, depending on the molecular weight and the transition temperature.
PDF
