EARLY ASSESSMENT OF CYTOSTATIC DRUG RESPONSE

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DESCRIPTION: (adapted from the proposal) A non-invasive imaging technique to assess treatment response early in the course of cancer therapy would have immediate clinical impact. Early assessment is particularly relevant to the newer biological treatments involving cytostatic (in contrast to cytolytic) drugs, where the evaluation of treatment response is often protracted over weeks to months. Namely, a long period of observation is often required before there are significant changes in the patient`s clinical status or in the magnetic resonance (MR) or computerized tomographic (CT) scans. This impacts on the assessment of treatment response based on `time to progression of disease`, and on treatment response based on `survival`. Furthermore, these criteria (clinical end points) provide little prognostic information that is useful in the clinical management of individual patients. The specific objective of this proposal is to compare noninvasive positron emission tomographic (PET) imaging to standard clinical and MR/CT criteria for evaluating treatment response to a cytostatic drug (SU101, a PDGF receptor antagonist). This is a pilot study of 10 patients with high grade, malignant brain tumors (glioblastoma multiforme) at time of first relapse. The broader objective is to address whether imaging a change in tumor proliferative activity (and/or glucose metabolism) early in the course of treatment with cytostatic drugs has prognostic value. Namely, does a decrease in the proliferative or metabolic activity of tumors occur early (after one or two course of therapy) in patients that are subsequently confirmed to be treatment responsive by standard criteria? This application proposes to evaluate whether a change in tumor proliferation assessed by [124I]-labeled iododeoxyuridine (IUdR) PET imaging {or a change in tumor metabolism measured by [18F]-labeled fluorodeoxyglucose (FDG) has potential for establishing a new criterion for defining early treatment response.