Abstract
5556 Background: NPC is traditionally treated with chemoradiation followed by chemotherapy. Ongoing trials are exploring neoadjuvant chemotherapy in NPC. Hypoxic head and neck cancers are known to be less sensitive to radiation. It is unknown if reversal of hypoxia prior to radiation results in better tumor control with radiation or if hypoxia is merely a marker of inherent radiation resistance. Data in other cancer settings suggest that both chemotherapy and bevacizumab might reduce tumor hypoxia. F-18 misonidazole (FMISO) is a hypoxia detection agent based upon misonidazole’s covalent binding to cellular macromolecules when reduced. Tumor/blood pool ratios of FMISO can be used to assess for relative tumoral hypoxia. Methods: Patients with locoregionally advanced or oligometastatic NPC were enrolled on an IRB approved clinical trial of a single dose of bevacizumab, followed by 3 cycles of therapy with concurrent cisplatin, docetaxel, 5-fluorouracil and bevacizumab (TPFB), followed by chemoradiation with cisplatin and bevacizumab. Hypoxia imaging was attempted using FMISO PET scans at baseline, following the single dose of bevacizumab and after the completion of TPFB in order to assess the feasibility of detecting baseline tumor hypoxia and changes in tumor hypoxia. The primary endpoint of the trial was progression free survival with early stopping rules for safety and feasibility concerning FMISO PET imaging. Results: Five patients have completed treatment and hypoxia imaging as of 1.31.11. Two achieved a CR and 3 a PR to TPFB, and all patients achieved a CR after completing chemoradiation. All patients remain alive without evidence of disease. Treatment was completed as planned without delay in all patients without SAEs. There were no clinically significant bleeding episodes. Baseline tumor/blood pool ratios of FMISO by PET imaging ranged from 1.2 to 2.2 without significant change in the ratios following bevacizumab and TPFB administration, despite large volume reduction in tumor mass. Conclusions: Details concerning FMISO imaging and implications for in vivo hypoxia imaging during cancer treatment will be presented. Further clinical testing of hypoxia detecting agents is warranted.
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