Clinical Oncology

[The role of early clinical studies in oncology]

KERPEL-FRONIUS Sándor

FEBRUARY 10, 2018

Clinical Oncology - 2018;5(01)

[Although the basic theory of the early development of different drug groups is identical, due to their various pharmacological characteristics the design of the studies, the starting safe dose and the selection of the pharmacologic and therapeutic end-points show signifi cant differences. The development process of drugs is usually divided into two functionally different parts, the learning and the confi rming phases, respectively. The aim of the fi rst part is the description of the suggested targets, the mechanism of action in humans and the characterization of the drug-linked biomarkers. This section contains the microdose (phase 0), phase I and II studies. The end-point of this part is the proof of the underlying concept which was developed on the basis of the non-clinical studies. According to the internationally accepted terminology, this strategically important point is called the Proof of Concept (POC). Upon POC it has to be decided whether the drug-candidate possesses those qualities which make it worthwhile to perform human phase III studies, treating the statistically required number of patients for proving the good therapeutic effi cacy and safety of the drug. This section of the drug development is called the confi rmatory phase. The use of highly sophisticated technology opened the possibility to apply microdoses in humans for studying the pharmacokinetics and pharmacodynamics of new drugs as well as the characteristics of human biomarkers at very low, harmless drug doses. This approach made possible to draw important conclusions on the usefulness of biomarkers for the clinical practice even following the fi rst drug-application. The planning of phases I and II studies, the calculation of the applicable doses, the selection of the pharmacologic and therapeutic end-points, the use of biomarkers, are all based on the concept of translational medicine and are essentially dependent on the results obtained both in animal experiments and human microdose studies.]

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[SABCS 2017 has been a 40-year jubilee conference with festive appearance and content. The anniversary provides possibility to look back: today we fi nd the knowledge and practice as of twenty years ago schematic and rough while the changes are overwhelming. Therapy became colorful and personally. There is need for precisious care which means consideration all patient and tumor features when surgical or medical therapy, radiotherapy or even diagnostic issues are decided - this has been the most important message of the conference this year. The Symposium always provides the most modern and breakthrough approaches and attitude that support advancement in patient care.]

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[Recent breakthroughs in the fi eld of organ transplantation and oncology have challenged existing views, and necessitate the revision of several tumor-related issues in transplantation. The need for expanding the donor pool raises the question of how and when it is plausible to transplant the organs of a donor with a history of cancer, such that the risk of tumor inoculation and manifestation due to the graft would be minimal for the recipient. Another point to consider is whether it is acceptable to transplant a recipient with a history of a malignant tumor, and if yes, how much tumor-free survival time is required as a minimum before the transplant. Transplanted patients live longer as a result of modern immunosuppressive therapy. However, the risk of malignant tumors increases proportionally to the length of the immunosuppressed state: their incidence may be as much as 20-30% in the long term. The signifi cance of „de novo” posttransplant tumors is highlighted by the fact that they are among the leading causes of death in transplant patients. Taken together, malignant diseases pose a serious problem from several aspects, the solution for which requires close teamwork of experts in oncology and transplantation, and the integration of up-to-date knowledge in the process of making a therapeutic decision, tailored individually for the patient.]

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