[Principles and practice of clinical phase II studies]

Primary aim of the phase II study is to assess the antitumoral activity of new agents and in a second step their therapeutic effectivity. In addition, toxicity will be assessed. For cytotoxic agents, tumor shrinkage, the socalled response, is the dominant parameter for evaluation. Nowadays, the Response Evaluation Criteria in Solid Tumors (RECIST) are widely used. For cytostatic agents with preponderance of tumor growth inhibition, the time interval to tumor progression has been proven to be the more relevant parameter. In addition, further parameters of clinical benefit are to be tested. Whether or not a parameter can be used as surrogate for a relevant endpoint has to be validated for each of them separately. For the assessment of toxicity, the Common Terminology Criteria for Adverse Events (CTCAE; current version 3.0) are used. The early phase II study allows to assess cumulative toxicity, pharmacokinetics, and pharmacokinetic-pharmacodynamic interactions. The socalled late phase II study focuses on the assessment of the therapeutic effect of both single-agent therapy and combinations of drugs and/or therapeutic modalities. The phase II study continues to be of high impact, especially for the testing of substances with well-defined molecular targets to identify those which will consecutively yield positive phase III trials out of a plethora of substances.