Targeting the IGF-1R in prostate and colorectal cancer: reasons behind trial failure and future directions

IGF-1Rs enact a significant part in cancer growth and its progress. IGF-1R inhibitors were encouraged in the early trials, but the patients did not benefit due to the unavailability of predictive biomarkers and IGF-1R system complexity. However, the linkage between IGF-1R and cancer was reported three decades ago. This review will shed light on the IGF-1R system, targeting IGF-1R through monoclonal antibodies, reasons behind IGF-1R trial failure and future directions. This study presented that targeting IGF-1R through monoclonal antibodies is still effective in cancer treatment, and there is a need to look for future directions. Cancer patients may benefit from using mAbs that target existing and new cancer targets, evidenced by promising results. It is also essential that the academician, trial experts and pharmaceutical companies play their role in finding a treatment for this deadly disease.

Interpretable Trials: Is Interpretability a Reason Why Clinical Trials Fail?

Background: There are clinical trials using composite measures, indices, or scales as proxy for independent variables or outcomes. Interpretability of derived measures may not be satisfying. Adopting indices of poor interpretability in clinical trials may lead to trial failure. This study aims to understand the impact of using indices of different interpretability in clinical trials.Methods: The interpretability of indices was categorized as: fair-to-poor, good, and unknown. In the literature, frailty indices were considered fair to poor interpretability. Body mass index (BMI) was highly interpretable. The other indices were of unknown interpretability. The trials were searched at clinicaltrials.gov on October 2, 2018. The use of indices as conditions/diseases or other terms was searched. The trials were grouped as completed, terminated, active, and other status. We tabulated the frequencies of frailty, BMI, and other indices.Results: There were 263,928 clinical trials found and 155,606 were completed or terminated. Among 2,115 trials adopting indices or composite measures as condition or disease, 244 adopted frailty and 487 used BMI without frailty indices. Significantly higher proportions of trials of unknown status used indices as conditions/diseases or other terms, compared to completed and terminated trials. The proportions of active trials using frailty indices were significantly higher than those of completed or terminated trials.Discussion: Clinical trial databases can be used to understand why trials may fail. Based on the findings, we suspect that using indices of poor interpretability may be associated with trial failure. Interpretability has not been conceived as an essential criterion for outcomes or proxy measures in trials. We will continue verifying the findings in other databases or data sources and apply this research method to improve clinical trial design. To prevent patients from experiencing trials likely to fail, we suggest further examining the interpretability of the indices in trials.

Chronic endometritis in in vitro fertilization failure patients

Introduction: Chronic endometritis (CE) is a common cause of infertility in asymptomatic patients and its diagnosis and treatments improved assisted reproduction technique outcome in most of the specialized centers. Diagnosis of CE in endometrial biopsy by Hematoxylin and Eosin (H&E) stain is hard to identify chronic inflammatory cells from the stroma and the use of plasma cells-specific stains is helpful. Aim of the work: Evaluation of the use of CD138 in the identification of plasma cells in endometrial biopsy of patients with previous IVF trial failure. Material and methods: Hysteroscopic and curettage endometrial biopsies from fifty-five females with previous IVF trial failure were stained with H&E and CD138 immunostaining for detection of plasma cells. Results: Plasma cells were identified in 52.7% of cases by H&E and in 6/55 by CD138 immunostaining. CD138 is more sensitive in detecting plasma cells in endometrial biopsy than H&E stain. There was a significant statistical correlation between CE and abnormal uterine bleeding, abortion and primary infertility (p > 0.5). Conclusion: Diagnosis of CE is helpful in infertility patients with IVF trial failure to improve the outcome of the maneuver. CD138 is more sensitive for plasma cells specially in endometrial biopsies than H&E.