Evaluation of the Activity of Temsirolimus With FDG-PET and FLT-PET in Patients With Renal Cell Cancer
The prognosis of metastatic renal cell carcinoma (mRCC) patients has improved the last
couple of years, due to the treatment with angiogenesis inhibitors and mTOR inhibitors.
First line and second line therapy is nowadays standard. However, responses on third or
fourth line therapy, in RCC patients participating in phase I studies have been observed. As
yet the optimal sequence of therapeutic agents in mRCC is not known and data on progression
free survival of third or fourth line treatment is not available. More and more patients
with metastatic RCC will receive multiple sequential treatments. A large proportion of those
patients will remain in a good condition and have a good quality of life. Those are the
candidates for new lines of therapy.
In the evaluation of new treatments the difficulty lies in the way of assessment of activity
of new drugs. In the past, chemotherapy induced real volume responses, whereas with the new
targeted agents volume reponse may take a long period of time (more than 6 months is not
exceptionial), or will never induce a real decrease in tumor volume, while the patient may
benefit from a long period of stable disease. All these new drugs are costly and not without
side effects, and therefore there is an urgent need for new end points of therapy, better
reflecting the activity of the drug.
In first line poor prognosis metastatic RCC patients mTor inhibition with temsirolimus has
become standard therapy based on an improvement in PFS and OS. Also for temsirolimus RECIST
criteria have been used. However, by using the RECIST criteria for the evaluation of
efficacy only the change in tumour volume is assessed. Temsirolimus is an antiproliferative
anti cancer drug and proliferation might be assessed by FLT PET or FDG PET.
Until now only very limited data have been published on the role of FDG PET and FLT PET
after mTor inhibitors. FLT PET seems promising in mice glioblastoma in mice treated with
mTor inhibitors. Another very recent paper reports the value of FDG PET as suurogate marker
of everolimus activity, also in mice. Only one clinical study in which FDG PET was used in
patients treated with mTor inhibitors had included patients with a mixture of diagnoses.
Therefore, we propose to investigate in a systematic way whether molecular imaging with
FLT-PET and/or FDGPET is a better predictor of response and progression free survival (PFS)
than evaluation by standard anatomical imaging by CT-scan in RCC patients treated with
temsirolimus. Furthermore, we propose to investigate the optimal way of assessment of
molecular characteristics of the tumor (metabolism, proliferation) by comparing FLT-PET with
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluation of the FLT-PET and FDG-PET
Measurement of 18F-FLT-PET-signal and FDG-PET-signal (ROI analysis and SUVmax calculation), and signal changes during treatment with temsirolimus (percentage change in SUVmax) Correlation of 18F-FLT-PET and FDG-PET before, and signal changes during treatment with treatment outcome (clinical response and PFS).
before and during treatment
C.M.L. van Herpen, Md PhD
University Medical Centre Nijmegen
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)