A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma.

BACKGROUND: DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with ≥1 prior tyrosine kinase inhibitor. METHODS: In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1-4 of a 28-day cycle, for two cycles. Primary endpoint was overall response rate; progression-free survival (PFS) and safety were secondary endpoints. RESULTS: 35 patients were enrolled and treated. One patient (2.9 %) had a response to treatment. The response was dramatic (84 % reduction in tumor burden by RECIST 1.0 criteria) and durable (patient remains free of progression 2 years after completing therapy). Whole exome sequencing of this patient's tumor revealed missense mutations in the mTOR and FGFR2 genes which is of interest because nucleolin is known to upregulate mTOR pathway activity by enhancing AKT1 mRNA translation. No other responses were seen. Thirty-four percent of patients had an AS1411-related adverse event, all of which were mild or moderate. CONCLUSIONS: AS1411 appears to have minimal activity in unselected patients with metastatic RCC. However, rare, dramatic and durable responses can be observed and toxicity is low. One patient in this study had an excellent response and was found to have FGFR2 and mTOR mutations which will be of interest in future efforts to discover and validate predictive biomarkers of response to nucleolin targeted compounds. DNA aptamers represent a novel way to target cancer cells at a molecular level and continue to be developed with a view to improving treatment and imaging in cancer medicine.

Implementing a referral to telephone tobacco cessation services in Louisiana community pharmacies: a pilot study.

BACKGROUND: With one of the highest rates of tobacco dependence in the nation, Louisiana has been searching for economical and effective methods for assisting patients in cessation efforts. Community pharmacists are in an excellent position to promote tobacco cessation due to their availability to patients. The "Ask-Advise-Refer" model is a short intervention in which patients desiring to quit smoking are referred to free tobacco cessation telephone counseling services. OBJECTIVE: To evaluate the implementation of the Ask-Advise-Refer model in a sample of Louisiana pharmacies and identify barriers experienced by pharmacists when identifying and referring appropriate patients. METHODS: Nine pharmacists from across the state implemented the Ask-Advise-Refer model in their community pharmacies. Each pharmacist submitted a weekly tally sheet consisting of number of patients asked about tobacco dependence, number of patients not ready to quit, number referred to tobacco cessation telephone counseling, number enrolled in study, and amount of time involved with interventions. Additionally, participating pharmacists completed a self-administered survey at the completion of the pilot study to determine opinions on barriers to widespread implementation of the program. RESULTS: Over a 6-month period, the 9 pharmacists asked 5429 patients about tobacco dependence. Of the 657 self-identified tobacco-dependent patients, 478 (72.8%) were not ready to quit, and 179 (27.2%) indicated that they were ready to quit tobacco in the next 30 days. Of the patients ready to quit, 169 (94.4%) were referred to telephone counseling services to assist in their cessation efforts. CONCLUSIONS: Louisiana community pharmacists have the ability to screen and identify tobacco-dependent patients ready to quit tobacco use, but barriers exist that prevent a large number of these patients from being referred to available, free cessation counseling.