A Pilot Trial Evaluating Zoledronic Acid Induced Changes in [<Superscript>18</Superscript>F]FMAU-Positron Emission Tomography Imaging of Bone Metastases in Prostate Cancer

Purpose

We conducted a pilot trial utilizing [¹⁸F]FMAU [1-(2′-deoxy-2′-[¹⁸F]fluoro-β-d-arabinofuranosyl thymine] as a tumor tracer in positron emission tomography (PET) and evaluated its reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM).

Procedures

Eligible patients had CRPC with radiographic evidence of BM and creatinine clearance >30 ml/min. Two baseline [¹⁸F]FMAU-PET scans (about 1 week apart, range 2–12 days) were obtained for testing reproducibility. Zoledronic acid 4 mg was infused over 15 min within 1 week after second scan and a third PET scan was obtained 7 days later. The bony lesion with the highest uptake on the first scan was compared with later scans. Bone turnover markers and prostate-specific antigen (PSA) were obtained pre- and post-therapy. PET response was defined as decline in SUVmean of ≥15 % after zoledronic acid.

Results

Eleven patients were evaluated, median age was 65 years, five were African-American and six were Caucasian, and median PSA level was 36.3 ng/ml (range 1.0–1209.3). Notably, the range of absolute percent SUVmax changes varied between 0.77 and 54.7, and only nine measurements were greater than one (1.09–2.19). Zoledronic acid did not appreciably change FMAU uptake. No clinical response was noted. Urine N-telopeptide (NTx) was markedly decreased in all patients after zoledronic acid and serum bone-specific alkaline phosphatase (BSAP) registered a modest change. Urine NTx correlated more closely with SUV max than serum BSAP.

Conclusions

FMAU tracer was able to detect bone metastases in CRPC patients but uptake was highly variable in bony lesions. Zoledronic acid did not produce an appreciable change in scans. Future investigations of FMAU tracer as a marker of early response in CRPC is recommended.

     

Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy

BACKGROUND.

The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression‐free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.

METHODS.

Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead‐time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.

RESULTS.

In total, 1158 patients were included. The median follow‐up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log‐rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42‐3.84) and 2.96 (95% confidence interval, 2.39‐3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.

CONCLUSIONS.

PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents. Cancer 2011;. © 2010 American Cancer Society.