Efficacy of nintedanib and docetaxel in patients with advanced lung adenocarcinoma treated with first-line chemotherapy and second-line immunotherapy in the nintedanib NPU program.

PURPOSE: Both nintedanib/docetaxel and anti-PD-1/PD-L1 immunotherapies have demonstrated efficacy as second-line treatment of patients with advanced lung adenocarcinoma. This is the first report on the efficacy of the nintedanib/docetaxel combination following first-line platinum-based chemotherapy and subsequent immunotherapy in a real-world setting. METHODS/PATIENTS: From May 2014 to December 2015, 390 patients in 108 Spanish centres enrolled in the nintedanib named patient use program. Inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. The objective was to evaluate the efficacy of the nintedanib/docetaxel combination in patients who also received immunotherapy. RESULTS: Eleven patients met the inclusion criteria; with a median age of 67 years. PD-L1 expression was positive in six patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (95% CI 1.9-4.6). Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) or nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (95% CI 0-6.1). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. Median PFS of nintedanib/docetaxel was 3.2 months (95% CI 1.9-4.5). Best response was partial response in four patients (36%), stable disease in five patients (46%), and progressive disease in two patients (18%), for an ORR of 36% and a DCR of 82%. CONCLUSION: Our experience suggests an encouraging efficacy of nintedanib/docetaxel in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy, reinforcing the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma.

Morphological and physiological changes exhibited by a Cd-resistant Dictyosphaerium chlorelloides strain and its cadmium removal capacity.

Changes induced on freshwater microalga Dictyosphaerium chlorelloides (Dc(wt)) acclimated in the laboratory until their survival in culture media enriched with cadmium 100 µM have been studied. Cadmium removal by living cells of this Cd-resistant (Dc(CdR100)) strain was tested in cultures exposed to 100 µM Cd during 30 days. Cell dimensions were measured under light microscopy, and cell growth was studied. Photosynthetic yield (ΦPSII) was analyzed and the photosynthetic oxygen development and respiration response was obtained. Results show that Dc(CdR100) strain exhibited significant cell morphology changes in comparison to Dc(wt) cells, which affected both surface area and cell biovolume. Malthusian fitness analysis showed that Dc(CdR100) strain living in Cd-enriched culture had developed a lower capacity of nearly 50% growth, and its photosynthetic oxygen development and respiration response were significantly reduced in both light and dark photosynthetic phases. Dc(CdR100) strain showed a very high capacity to remove cadmium from the aquatic environment (over 90%), although most of the removed heavy metal (≈70%) is adhered to the cell wall. These specific characteristics of Dc(CdR100) cells suggest the possibility of using this strain in conjunction with Dc(wt) strain as bioelements into a dual-head biosensor, and in bioremediation processes on freshwater polluted with Cd.

Interference of heavy metals on the photosynthetic response from a Cr(VI)-resistant Dictyosphaerium chlorelloides strain.

The successful selection of a particular type of bioelement and its association to the appropriate transducer determines the specificity of a biosensor. Therefore, from a strain of chloroficea Dictyosphaerium chlorelloides, modified in laboratory to tolerate high Cr(VI) concentrations, the possible interferences of other heavy metals on photosynthetic activity were studied. After exposing wild type and Cr(VI)-resistant cells to increasing Ag(+1), Co(+2), Hg(+2), Cr(+3), Cu(+2), Zn(+2), Fe(+3) and Cd(+2) concentrations, both photosynthetic quantum yields was compared. Photosynthetic electron transport rates were measured with a TOXY-PAM chlorophyll fluorometer, non-linear regression analysis of each of the toxicity tests was done, and means of both groups were compared using unpaired t test. The results show no significant differences between both cell types when they were exposed to Ag(+1), Co(+2), Hg(+2), Cr(+3), Cu(+2), Fe(+3) and Cd(+2) metal ions, and extremely significant differences (p < 0.0001) to Zn(+2) exposures. These results demonstrate the suitability of this Cr(VI)-resistant type D. chlorelloides strain as a suitable bioelement to be coupled to a biosensor based on dual-head microalgae strategy to detect and quantify Cr(VI) in water courses and waste water treatment plants. However, some disturbance may be expected, especially when certain analyte species such as zinc are present in water samples tested. The analysis of binary mixtures between Zn(+2) and other heavy metals showed a slight antagonistic phenomenon in all cases, which should not alter the potential Zn(+2) interference in the Cr(+6) detection process.