F-18-FDG PET/CT for Monitoring Treatment Responses to the Epidermal Growth Factor Receptor Inhibitor Erlotinib

Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-7371, USA.
Journal of Nuclear Medicine (Impact Factor: 6.16). 11/2011; 52(11):1684-9. DOI: 10.2967/jnumed.111.095257
Source: PubMed


Response rates of unselected non-small cell lung cancer (NSCLC) patients to the epidermal growth factor receptor inhibitor erlotinib are low and range from 10% to 20%. Early response assessments are needed to avoid costs and side effects of inefficient treatments. Here we determined whether early changes in tumor uptake of (18)F-FDG can predict progression-free and overall survival in NSCLC patients who are treated with erlotinib.
Twenty-two patients (6 men, 16 women; mean age ± SD, 64 ± 13 y) with stage III or stage IV NSCLC who received erlotinib treatment were enrolled prospectively. (18)F-FDG PET/CT was performed before the initiation of treatment (n = 22), after 2 wk (n = 22), and after 78 ± 21 d (n = 11). Tumor maximum standardized uptake values were measured for a maximum of 5 lesions for each patient. Tumor responses were classified using modified PET Response Criteria in Solid Tumors (use of maximum standardized uptake values). Median overall survival by Kaplan-Meier analysis was compared between groups using a log-rank test.
The overall median time to progression was 52 d (95% confidence interval, 47-57 d). The overall median survival time was 131 d (95% confidence interval, 0-351 d). Patients with progressive metabolic disease on early follow-up PET showed a significantly shorter time to progression (47 vs. 119 d; P < 0.001) and overall survival (87 vs. 828 d; P = 0.01) than patients classified as having stable metabolic disease or partial or complete metabolic response.
These data suggest that (18)F-FDG PET/CT performed early after the start of erlotinib treatment can help to identify patients who benefit from this targeted therapy.

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    • "The principle of using PET for (early) therapy evaluation has since been tested in numerous studies and settings, including conventional cytotoxic chemotherapy, radiotherapy and molecular-targeted therapy, that is EGFR tyrosine kinase inhibitors (Hoekstra et al., 2002; Mac Manus et al., 2005; van Baardwijk et al., 2007; Kong et al., 2007; Maziak et al., 2009; Benz et al., 2011). All studies conclude that PET is potentially useful for therapy planning and evaluation; however, larger controlled trials assessing the clinical effect is still lacking as is necessary standardization of SUV measurements (Weber & Figlin, 2007). "
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    • "Multiple studies demonstrate that PET/CT is more sensitive and specific than PET alone in evaluating the lung cancer since it provides combined morphological and functional information of the tumour.4–7 High accuracy of PET/CT has been observed in the early assessment of response to therapy, showing a close correlation between the reduction of tumour metabolic activity measured after a course of therapy and the clinical outcome of patients after the previewed cycles of therapy in patients in advanced stage.8–9 In early stage, Tumour Node Metastasis (TNM) staging system, it is still the most reliable prognostic factor to predict the outcome after surgery. "
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    • "18F-FDG PET has also been used successfully to assess tumor responses to targeted, predominantly cytostatic therapies, including imatinib [134, 135], gefitinib [136], erlotinib [137] (Fig. 3), and the B-Raf inhibitor PLX4032 [138] (Fig. 4). The prompt reduction of 18F-FDG tumor uptake in response to imatinib and gefitinib appears to be explained by a translocation of membrane-bound glucose transporters into the cytoplasm and thus their inactivation [139]. "
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