WILEX AG Receives Preliminary Results of
Phase 3 Trial With the Diagnostic REDECTANE®
MUNICH—The biopharmaceutical company WILEX AG was informed by the external clinical research organisation (CRO) that the results of the preliminary data of the phase 3 trial with REDECTANE® expected at the end of December have now been completed earlier than anticipated. The aim of the phase 3 REDECTANE study was to determine whether the combination of REDECTANE with positron emission tomography (PET) and computer tomography (CT) versus the standard use of CT alone could improve the diagnosis of renal masses. Sensitivity and specificity were the defined endpoints of the study. In order to avoid unnecessary surgery of renal masses in the future, a diagnostic agent should predict that clear cell renal cell cancer is not present (specificity).

The results of the study demonstrate that PET and CT with REDECTANE lead to an improved diagnosis in comparison to CT. The study endpoint specificity, the correct diagnosis that clear cell renal cell cancer is not present, was achieved with a highly statistical value (P < .001). The second endpoint, the correct diagnosis of clear cell renal cell cancer (sensitivity), came close to achieving statistical significance (P = .052 instead of P < .050). CT performed better with respect to sensitivity in the study than expected and than generally observed in clinical practice. The final patient data still need to be analyzed. Small changes can significantly impact the statistical results.

WILEX expects the final results in the first quarter of 2010 and plans to discuss these with external experts and to consult the process going forward with the FDA. Dr Paul Bevan, head of research and development and a member of the executive management board commented, “The preliminary data support our hypothesis that PET/CT with REDECTANE is superior to CT alone in the diagnosis of clear cell renal cell cancer. We are especially surprised at the superiority of REDECTANE to CT in the diagnosis that clear cell renal cell cancer is not present. This could avoid unnecessary surgery of renal masses in the future.”

Excess Body Weight Linked With More Than 100,000
New Cancer Diagnoses Each Year in the United States
According to estimates from the American Institute for Cancer Research (AICR), excess body weight may be re-sponsible for more than 100,000 new cancer diagnoses each year in the United States, including renal cell carcinoma.

Excess body weight is increasingly recognized as a risk factor not only for cancer development but also for worse outcomes after cancer treatment. Links have been established between excess body weight and cancers of the endometrium, esophagus, pancreas, kidney, breast (in postmeno-pausal women), and colorectum. There is also a probable link between excess body weight and gallbladder cancer.

Body mass index (BMI) is a commonly used (though imperfect) measure of body size. It involves a comparison of weight to height (weight in kilograms divided by height in meters squared). A BMI between 18.5 and 24.9 is generally considered healthy, a BMI between 25 and 29.9 is considered overweight, and a BMI of 30 or higher is considered obese. A report released by AICR estimated the number of cancers that could be prevented each year in the United States if everyone maintained a healthy body weight:

Reference:
AICR. New estimate: excess body fat alone causes over 100,000 cancers in US each year. Researchers present data linking obesity/overweight to higher cancer risk, poorer cancer survival. http://www.aicr.org/ site/ News2/1028460841?abbr=pr_&page=News Article&id=17333& news_iv_ctrl=1102. Accessed December 14, 2009.

 

 

Hemoglobin Levels Predict Outcomes With Bevacizumab
SAN FRANCISCO—Patients with advanced renal cell carcinoma who responded to angiogenesis inhibitor drugs also had higher hemoglobin levels, a researcher reported here. The finding suggested that hemoglobin responses might accurately predict outcomes with bevacizumab (Avastin), according to Lauren Harshman, MD, of Stanford University, at the American Society of Hematology meeting.

In a poster session, Dr Harshman presented data from a retrospective study of 12 patients with advanced kidney cancer who were treated off-label with bevacizumab, a monoclonal antibody that inactivates vascular endothelial growth factor (VEGF). She said this was the first human study to find increased hemoglobin as a consequence of anti-VEGF drug therapy. Other agents that target the VEGF pathway—such as sunitinib (Sutent) or sorafenib (Nexavar), which inhibit receptor signaling—tend to produce anemia because they inhibit pathways involved in red-cell production.

Earlier studies at Stanford found that mice with ultra-tight VEGF suppression showed increased liver production of erythropoietin and a corresponding increase in blood hemoglobin. That led the researchers to inquire whether hemoglobin level might be an indicator of successful VEGF suppression and, by extension, of improved clinical antitumor effect. In their review of clinical records, Dr Harshman and colleagues found that the mean progression-free survival for patients with a greater than 15% increase from baseline in hemoglobin levels was 8.2 months.

In contrast, patients whose hemoglobin did not rise that much with treatment had mean progression-free survival of just 3.1 months (P = .02). The median percentage rise was 12.3%, with a median time to initial increase of 35 days and a median time to maximal increase of 82 days. However, none of the patients included in the study achieved objective responses; the best outcome was stable disease in 8 patients. Dr Harshman reported that 11 of the 12 patients showed some increase in hemoglobin levels, which confirmed the researchers’ initial hypothesis on the correlation between VEGF suppression and red-cell stimulation.

Unexpectedly, some of the patients who showed significant hemoglobin increases and relatively good outcomes were taking low doses of sorafenib or sunitinib in addition to bevacizumab. These low doses were perhaps sufficient to boost VEGF signaling inhibition but not enough to induce anemia, according to Dr Harshman. She said the small number of patients included in the study and lack of information on a variety of potential confounding factors limit the study’s interpretation. She suggested that confirmation of the findings may be possible in ongoing phase 2 studies of bevacizumab in renal cell carcinoma. KCJ