FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.
BACKGROUND
Metastatic 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.


METHODS
Twenty 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.


RESULTS
Proliferative 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.


CONCLUSIONS
While 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.


BACKGROUND
ID: NCT00694096.
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. kevin.horn@hsc.utah.edu.|Department of Radiology, University of Utah, 30 North 1900 East #1A071, Salt Lake City, UT, 84132-2140, USA. kevin.horn@hsc.utah.edu.
Kevin P
KP
Horn
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. jeffrey.yap@hci.utah.edu.|Department of Radiology, University of Utah, 30 North 1900 East #1A071, Salt Lake City, UT, 84132-2140, USA. jeffrey.yap@hci.utah.edu.
Jeffrey T
JT
Yap
Department of Medicine, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr, Salt Lake City, UT, 84112-5550, USA. neeraj.agarwal@hci.utah.edu.
Neeraj
N
Agarwal
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. kathryn.morton@hsc.utah.edu.|Department of Radiology, University of Utah, 30 North 1900 East #1A071, Salt Lake City, UT, 84132-2140, USA. kathryn.morton@hsc.utah.edu.
Kathryn A
KA
Morton
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. kadrmas@ucair.med.utah.edu.|Department of Radiology, University of Utah, 30 North 1900 East #1A071, Salt Lake City, UT, 84132-2140, USA. kadrmas@ucair.med.utah.edu.
Dan J
DJ
Kadrmas
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. britney.beardmore@hci.utah.edu.
Britney
B
Beardmore
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 Thirteenth Street, Suite 2301, Charlestown, MA, 02129, USA. ributterfield@mgh.harvard.edu.
Regan I
RI
Butterfield
Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr, Salt Lake City, UT, 84112-5550, USA. kenneth.boucher@hci.utah.edu.
Kenneth
K
Boucher
Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Suite 6810, Salt Lake City, UT, 84112-5560, USA. john.hoffman@hci.utah.edu.|Department of Radiology, University of Utah, 30 North 1900 East #1A071, Salt Lake City, UT, 84132-2140, USA. john.hoffman@hci.utah.edu.
John M
JM
Hoffman
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D015224:Dideoxynucleosides; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000008:administration & dosage*; D019275:Radiopharmaceuticals; D000077210:Sunitinib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D007211:Indoles; D011758:Pyrroles; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C002854:alovudine; D000077210:Sunitinib