Abstract
BackgroundMetastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy.MethodsTwenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using 18 F-fluorodeoxyglucose (FDG) and 18 F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment.ResultsProliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline 18 F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1–2 weeks after initiating therapy.ConclusionsWhile preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials.Trial registrationID: NCT00694096
Highlights
Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment
One to six target lesions were identified per patient on clinical computed tomography (CT) or magnetic resonance imaging (MRI) using RECIST 1.0 size criteria [10] and evaluated with subsequent positron emission tomography (PET) imaging
Et al conducted a study in which patients were imaged with FLT-PET after either 2 or 4 weeks of treatment with sunitinib, this study focused on the effects of the standard drug holiday on tumor proliferation and revealed a significant increase in tumor proliferation off drug [30]
Summary
Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. FDG-PET has already shown efficacy for early response assessment in therapeutic trials, including sunitinib therapy in gastrointestinal stromal tumors [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
