Expert recommendations on the management of patients with metastatic castration-resistant prostate cancer who progress after CHAARTED or LATITUDE

Objective: Our aim was to provide practical recommendations on the management of patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel plus androgen-deprivation therapy (ADT) or abiraterone plus ADT. Methods: Systematic literature review (SLR), nominal group meeting, and Delphi process. A panel of 12 experts was established who defined the scope, users, and sections of the document. We performed an SLR in order to assess the efficacy and safety of available drugs in patients with mCRPC. Abstracts from the American Society of Oncology and European Society for Medical Oncology meetings were also examined. The results were discussed during an expert meeting in which 14 recommendations were generated. The level of agreement with the recommendations was also tested by 13 additional experts following the Delphi process. Recommendations were voted by means of scores ranging from 0 (total disagreement) to 10 (total agreement). We defined agreement when at least 70% of the experts voted ¿7. Next, we assigned a level of evidence and grade to the recommendation using the Oxford Centre for Evidence-based Medicine Levels of Evidence, following which the final document was drafted. Results: The literature search did not find any articles meeting the inclusion criteria. Finally, 13 out of 14 recommendations were accepted after two Delphi rounds (two were modified after the first round). They pertain to general and individual case-based treatment recommendations. Conclusions: In mCRPC patients who have progressed after docetaxel or abiraterone plus ADT in the metastatic hormone-sensitive prostate cancer setting, these recommendations may support treatment decision-making, due to the lack of evidence or other globally accepted sequencing algorithms

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

Background: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Methods: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Results: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. Conclusion: This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cytomorphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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