Sgambato and colleagues (2016) noted that the better understanding of immunology and anti-tumor immune responses have prompted the development of novel immunotherapy agents like PD-1 checkpoint inhibitors (anti-PD-1 and anti-PDL-1 antibodies) that improve the capacity of the immune system to acknowledge and delete tumors, including lung cancer. Currently, 2 anti-PD-1 (nivolumab and pembrolizumab) and 1 anti- PD-L1 (MPDL-3280A) agents are in advanced stages of development in advanced or metastatic NSCLC. Among these, nivolumab demonstrated a survival benefit versus docetaxel in refractory squamous NSCLC, reporting 41 % reduction in risk of death (median overall survival [OS]: versus months; ORR: 20 % versus 9 %), and better safety profile than standard-of-care chemotherapy (grade 3 to 4 adverse events: 7 % versus 55 %). However, the enhancement of immune response to cancer targeting specific immune regulatory checkpoints is associated with a toxicity profile different from that related to traditional chemotherapeutic agents and molecularly targeted therapies.
As you reduce below about 7 or 8mg you are into the region where your body has to make its own corticosteroid again. It isn't that the adrenals have packed up as many people think - it is the complex feedback system governing it all that has to settle down and it isn't just cortisol that is being adjusted - it is thyroid and sex hormones and other things too. Thyroid hormones shooting up and down also causes exhaustion - it's a real mix. Until they have fine-tuned themselves you can feel not only tired but also quite emotional and weepy. Not everyone has to deal with this - like everything else we are all different. However, one thing is certain; going VERY slowly over the bumps makes the journey less uncomfortable!
Variability in cortisol assays creates an additional problem with setting criteria for a normal response to ACTH that apply to all centers. Two studies comparing cortisol results obtained with different assays showed a positive bias of radioimmunoassays and immunofluorometric enzyme assays of 10 to 50 percent compared with a reference value obtained using isotope dilution gas chromatography-mass spectrometry. As a result, in one study, depending on the combination of assay and criterion used, between 0 and 100 percent of healthy volunteers would be considered to have a normal response to ACTH. This illustrates the difficulty of interpreting cortisol responses that are close to the cutoff point. (3)