Exposure-Response Analysis of Necitumumab Efficacy in Squamous Non-Small Cell Lung Cancer Patients.

We sought to describe the exposure-response relationship of necitumumab efficacy in squamous non-small cell lung cancer patients and evaluate intrinsic and extrinsic patient descriptors that may guide dosing. SQUIRE was a phase III study comparing necitumumab in combination with gemcitabine and cisplatin vs. gemcitabine and cisplatin alone in 1,014 patients. An integrated model for tumor size dynamics and overall survival was developed, where reduction in tumor size results in a decrease in survival hazard. The change in tumor size was characterized using linear growth and first-order shrinkage. Overall survival was described using a combination of a Weibull function and Gompertz function for the hazard, with dynamic tumor size being a predictor for the hazard. Although body weight resulted in higher clearance and lower exposure, simulations showed that an 800 mg flat dose provided optimal response regardless of body weight.

Urethritis in women attending an STD clinic.

Of an unselected group of 159 women attending a sexually transmitted diseases (STD) clinic 20% (32) had symptoms of urethritis. A positive correlation existed between the finding of more than 10 polymorphonuclear leucocytes (PMNL) per high-power field in the Gram-stained urethral smear and the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Conversely, these organisms were rarely isolated if no PMNL were present. Fewer cultures gave positive results for these organisms if micturition had occurred less than four hours before examination. C trachomatis was recovered from the urethra or endocervix in 29/150 (19 . 3%) and from the urethra alone in six women. In contrast, N gonorrhoea was never recovered from the urethra in the absence of endocervical infection. Of the 159 women 10% had bacteriuria due to non-sexually transmissible agents; 50% had asymptomatic bacteriuria. All, however, had other urethral pathogens isolated as well. Thus, sexually transmitted disease agents are highly prevalent in women attending an STD clinic who have signs and symptoms of urethritis. As in non-gonococcal urethritis in men, C trachomatis may be an important cause of urethritis in women.