SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer.

BACKGROUND: Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. PATIENTS AND METHODS: Patients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations. RESULTS: A total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified. CONCLUSION: The primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported. TRIAL IDENTIFIER: Clinicaltrials.gov NCT01750281.

Defining acceptable epidemiology ranges in donor populations based on the contamination risk of finished plasma-derived products.

BACKGROUND: For a given plasma-derived product, the risk of final product contamination by hepatitis B virus, hepatitis C virus and human immunodeficiency virus depends upon the epidemiology in the donor population, the virus load in a donation, the product yield and the effective virus reduction capacity in manufacturing. STUDY DESIGN AND METHODS: A Monte Carlo simulation model was developed to estimate the risk of virus contamination of a final product resulting from virus contamination of plasma pools for fractionation. The model was run for both source and recovered plasma at various incidence rates for the three viruses to determine virus loads in minipools and fractionation pools resulting from donations with virus levels below test sensitivities. Together with the virus reduction capacity and yield of a theoretical worst case plasma-derived product, the contamination risk in a final vial was calculated. RESULTS: Acceptable upper-bound centre-level incidence rates in the donor population (per donor centre) result in final products with very high margins of virus safety; the largest determinant of these 'Process Limits' is the virus reduction capacity of the manufacturing process. Short donation intervals and long inventory hold periods for source plasma compensates the lower incidence rates typically observed in recovered plasma donors. CONCLUSIONS: The model calculates process limits for epidemiological data at collection centres based on an appropriate margin of virus safety for final products. The model also takes into consideration the impact of different donor/donation management systems for source and recovered plasma on the number of low viraemic donations entering the plasma pool for fractionation.

School-based clinic use and other factors affecting adolescent contraceptive behavior.

Adolescent risk taking, preventive behavior, and contraceptive use were investigated using a self-administered questionnaire in a sample of 260 inner-city high school students targeted by a school-based health clinic. Multivariate models consisting of individual and environmental variables significantly predicted sexual activity and contraceptive use. Older age at first intercourse, higher number of welfare benefits received by the household (including Medicaid, food stamps, and free or reduced price lunch), and use of the school-based clinic were significant positive predictors of more frequent contraceptive use by adolescents. Results of our study suggest that programs may be having some success in encouraging and enabling sexually active adolescents to use contraception and to use it more consistently. Rigorous program evaluations should help program planners and policy makers design and refine adolescent pregnancy-prevention efforts.

PIP: Adolescent risk taking, preventive behavior, and contraceptive use were investigated using a self-administered questionnaire in a sample of 260 inner-city high school students targeted by a school-based health clinic. Multivariate models consisting of individual and environmental variables significantly predicted sexual activity and contraceptive use. Older age at 1st intercourse, higher number of welfare benefits received by the household (including Medicaid, food stamps, and free or reduced price lunch), and use of the school-based clinic were significant positive predictors of more frequent contraceptive use by adolescents. Results of the study suggest that programs may be having some success in encouraging and enabling sexually active adolescents to use contraception and to use it more consistently. Rigorous program evaluations should help program planners and policy makers design and refine adolescent pregnancy-prevention efforts. The sample was drawn from a large urban high school in Texas, one of 7 schools targeted by a comprehensive school-based clinic.

Integrated school and community programs.

Collaboration and coordination among school nurses, health teachers, guidance counselors, food service directors, principals, administrators, parents, and community agencies have the potential to upgrade school health programs. Benefits derived from an integrated school and community program are documented. Three models that have effectively brought together schools and community agencies are described.