Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer

Maintenance monotherapy with the poly(ADP-ribose) polymerase inhibitor olaparib significantly prolongs progression-free survival over placebo in patients with platinum-sensitive relapsed serous ovarian cancer, with greatest benefit seen in patients with a BRCA1/2 mutation (BRCAm). Preservation of health-related quality of life (HRQoL) is important during maintenance therapy; we evaluated the effect of olaparib on HRQoL in this Phase II trial (NCT00753545, Study 19).status: publishe

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

Background: VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings: Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion: Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab

Vertical distributions of chlorophyll in deep, warm monomictic lakes

The factors affecting vertical distributions of chlorophyll fluorescence were examined in four temperate, warm monomictic lakes. Each of the lakes (maximum depth >80 m) was sampled over 2 years at intervals from monthly to seasonal. Profiles were taken of chlorophyll fluorescence (as a proxy for algal biomass), temperature and irradiance, as well as integrated samples from the surface mixed layer for chlorophyll a (chl a) and nutrient concentrations in each lake. Depth profiles of chlorophyll fluorescence were also made along transects of the longest axis of each lake. Chlorophyll fluorescence maxima occurred at depths closely correlated with euphotic depth (r 2 = 0.67, P < 0.01), which varied with nutrient status of the lakes. While seasonal thermal density stratification is a prerequisite for the existence of a deep chlorophyll maximum (DCM), our study provides evidence that the depth of light penetration largely dictates the DCM depth during stratification. Reduction in water clarity through eutrophication can cause a shift in phytoplankton distributions from a DCM in spring or summer to a surface chlorophyll maximum within the surface mixed layer when the depth of the euphotic zone (z eu) is consistently shallower than the depth of the surface mixed layer (z SML). Trophic status has a key role in determining vertical distributions of chlorophyll in the four lakes, but does not appear to disrupt the annual cycle of maximum chlorophyll in winter.David P. Hamilton, Katherine R. O’Brien, Michele A. Burford, Justin D. Brookes and Chris G. McBrid