"Real world" treatment of metastatic renal cell carcinoma in a joint community-academic cohort: progression-free survival over three lines of therapy.

BACKGROUND: New targeted therapeutics approved for metastatic renal cell carcinoma (mRCC) offer multiple options in each line of therapy; however, there are few prospective data beyond the first-line settings, and overall comparative effectiveness data are limited. In the targeted therapy era, progression-free survival (PFS) has been the most common regulatory end point for demonstrating the benefit of new therapies. PATIENTS AND METHODS: Drawing on a joint community-academic retrospective mRCC registry, we analyzed all patients who had undergone at least 1 line of systemic therapy (N = 325) for PFS. Patients were grouped according to treatment choice (sorafenib, sunitinib, temsirolimus, everolimus, and "other") for up to 3 lines of therapy. PFS by treatment choice and line of therapy was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: PFS was longest in patients treated with sunitinib in the first and second lines of therapy. First-line PFS for sorafenib, sunitinib, temsirolimus, everolimus, and "other" was 6.9, 8.9, 4.2, not analyzed (too few patients), and 10.8 months, respectively. Second-line PFS was 4.6, 7.0, 3.2, 3.8, and 4.1 months, respectively. Third-line PFS was 4.5, 4.6, 9.9, 4.2, and 2.9, months, respectively. The risk of progression in patients treated with temsirolimus was about twice that of patients treated with sunitinib in the first and second lines of therapy. CONCLUSION: Patients treated with sunitinib had the longest PFS in the first and second lines of therapy. PFS from practice-based data appear consistent with trial-based expectations; however, practice variation was still evident.

Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab.

PURPOSE: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab. EXPERIMENTAL DESIGN: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m(2) i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m(2) orally twice daily, days 1-14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45-0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44-0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71-1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). CONCLUSION: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions.

Patient and practice impact of capecitabine compared to taxanes in first-/second-line chemotherapy for metastatic breast cancer.

BACKGROUND: Oral chemotherapy regimens have emerged as comparably effective to intravenous regimens with the potential for less resource utilization, fewer treatment side effects and a better quality-of-life outcome. The objective of this retrospective chart review was to examine these issues among patients who received single-agent taxane therapy vs. single-agent capecitabine for first- or second-line treatment of metastatic breast cancer (MBC) METHODS: Data from the medical charts of 61 patients who received single-agent capecitabine, docetaxel, or paclitaxel therapy were supplemented with data from the 38-item Patient Care Monitor (PCM) survey of symptom burden and quality of life, prospectively collected during chemotherapy. The endpoints were PCM index scores, hospitalization during treatment, and the number of clinic visits during treatment. RESULTS: The sample was 75% Caucasian, 16% African-American, with a mean age of 59.4 years. Taxane-treated patients had more clinic visits than capecitabine patients, were more likely to have been hospitalized during treatment, and had worse treatment side effects. Controlling for depression, infusion-treated patients reported greater acute distress at the start of therapy than those on oral medication. CONCLUSION: Capecitabine for MBC was associated with a more favorable outcome regarding treatment side effects and quality of life, with reduced resource burden to patients and providers. Physicians may have differentially selected patients with greater depressive symptoms for capecitabine therapy.

Behavioral sleep medicine: a historical perspective.

Behavioral sleep medicine (BSM) has recently emerged as a subspecialty area within the broader field of sleep medicine. Certain commonly used treatment approaches in BSM were first pioneered in the 1930s, and this article traces the developments within BSM to current practice. Important innovations include the expansion of BSM beyond the treatment of insomnia to include treatment of pediatric sleep disorders, circadian rhythm disorders, parasomnias, as well as desensitization procedures for patients undergoing treatment with nasal continuous positive airway pressure (CPAP).