Disappointingly, trials of single-agent inhibitors of IGF-1R and downstream targets have generally shown only modest clinical responses (Jin et al, 2013).
To date, these combinations have led to only modest increases in clinical response.
Hitherto, patients treated with FLT3 inhibitors have, with the possible exception of AC220, shown only modest and transient clinical response.
SS1P is an immunotoxin consisting of an antimesothelin antibody variable fragment linked to a cytotoxic fragment of Pseudomonas exotoxin A. A Phase I trial including 16 patients with mesothelioma showed that SS1P was well tolerated up to 25 μg/kg/day × 10 days with modest clinical activity and minor responses, and that two mesothelioma patients had symptomatic improvement.
The clinical response was modest (6 patients out of 20 (30%) had overall stable disease) and the tolerability was good [ 53].
One trial using tumour necrosis factor-alpha-matured, monocyte-derived DCs pulsed with MUC1 or HER-2/ neu elicited peptide-specific anti-tumour responses, but the overall clinical response was modest [ 100].
Initial treatment with oral prednisolone (2 mg/kg/day) partially improved the rash and the patient's general well-being; anakinra (2 mg/kg/day) elicited a partial clinical response and modest steroid-sparing effect, but his clinical symptoms and serum amyloid A (SAA) levels were never well controlled.
Trials have also been conducted with a chimeric BR96-doxorubicin conjugate (SGN-15) in a range of cancer patients with some modest clinical activity, but some immune responses towards the BR96-doxorubicin conjugates were noted [22].
This is of real interest because the clinical response to Kineret is modest and might be explained by these circumstances.
However, there have been relatively few controlled clinical trials on antidepressant therapy for depression in AD and clinical response is generally poor to modest [ 59– 64].
