This design might be more suitable for late-stage phase 1 studies conducted in patient populations more likely to benefit from the investigational product. The development

of a monoclonal antibody also poses challenges with regard to its administration. Infusion-related reactions (IRRs) are a common side-effect of antibodies that can lead to interruption and termination of the therapy and can even result in fatalities in extreme cases. The Selleck AVL301 implementation of prophylactic measurements such as H1- and H2-blockers, steroids, and paracetamol or acetaminophen and the prolongation of the infusion might help to alleviate the incidence and severity Inhibitors,research,lifescience,medical of IRRs, but any implementation of such measures in phase 1 trials influences the further development of the compound substantially.5 Vast experience is required to carefully manage the prevention and treatment of such IRRs. Another challenge in the conduct of scientifically sound phase 1 trials is the analysis of surrogate markers from tumor tissue. The collection of fresh tissue often requires Inhibitors,research,lifescience,medical study-specific biopsies. Paraffin-embedded tumor blocks

Inhibitors,research,lifescience,medical are easier to obtain, although pathology institutions not involved in the clinical study are frequently reluctant to provide such samples for reasons related to their standard operating procedures or data protection laws. Every effort should be made to obtain such material, if its analysis can provide useful information concerning the definition of patient populations Inhibitors,research,lifescience,medical suitable for treatment with the investigational product and for the evaluation of the RP2D in the absence of an MTD.6 This trend towards personalized medicine in which tumor tissue from each patient is precisely defined might reduce the importance of the histology. The future testing of a combination of targeted molecules as opposed to classical cytotoxic agents creates a paradigm shift in the definition of the phase 1 patient population in oncology. While a rather heterogeneous cancer population Inhibitors,research,lifescience,medical was included in phase

1 trials in the past, the twenty-first century calls for rather precisely defined cancer patients with very specific tumor types. This ALOX15 approach was first used with receptors such as estrogen, progesterone, HER2, or EGFR,7 for which tumor tissue is stained for the expression of various proteins in parallel. There is clear evidence that triple-negative breast cancer patients have a different prognosis and require a different therapeutic approach than hormone receptor-positive and/or HER-positive tumors.8 Also, the qualitative definition of targets influences treatment approaches. For example, kras-mutant colorectal cancer is resistant to treatment with the EGFR antibody cetuximab, but kras-wild-type tumor tissue responds rather well to the treatment with this antibody.