No abstract

9505 Background: AP23573 is an mTOR inhibitor that has shown anti-tumor activity in phase 1 clinical trials, particularly in patients with advanced sarcomas. Given this observation, this phase 2 trial was undertaken to assess further the efficacy and safety of AP23573 across various sarcoma subtypes. Methods: Advanced sarcoma pts, with no restrictions on prior therapies, were enrolled into 4 cohorts based on histologic subtype, in a phase 2 trial with Simon’s 2-stage design. AP23573 (12.5 mg, i.v.) is administered for 5 days every 2 wks. Efficacy is assessed using RECIST guidelines, with clinical benefit response (CBR) defined as complete or partial response (PR) or stable disease (SD) for at least 16 wks duration. For each cohort, treatment was defined as successful if the proportion of patients with CBR was ≥ 25%. Studies of potential predictive markers of response include 18FDG-PET imaging, analysis of mTOR pathway proteins in tumoral tissue, and measurement of plasma cytokines and angiogenic factors. Results: In total, 216 pts were enrolled as all cohorts met criteria to enter Stage 2 of the trial. Of these pts, 213 were treated (106 M/107 F) (age 17–79 yrs, median 50 yrs). Most frequent related adverse events included mucositis, rash, hyperlipidemia, fatigue, and thrombocytopenia. Preliminary response data for 193 evaluable pts are available: overall 54 (28%) had CBRs, including 5 PRs (3 pts with osteo, 1 with spindle cell of bone, and 1 with MFH). Twenty of 76 pts (26%) imaged with PET had rapid induction of partial metabolic responses following 3 to 5 days of study treatment. Conclusions: Initial assessments from this trial show that single-agent AP23573 is well tolerated and has efficacy in pts with advanced sarcomas that warrants evaluation in phase 3. Analysis of the potential utility of FDG-PET and a broad set of candidate biomarkers continues. Enrollment is complete, and pt treatment and follow-up are ongoing. [Table: see text] [Table: see text]

were created that demonstrate anticipated weight loss by percentile over 72 hours (vaginal delivery) or 96 hours (cesarean delivery). Important limitations of the study included nonstandardized scales, lack of information about why formula was initiated, and the time frame that weights had been recorded may not catch the actual weight nadir for all infants.In 2003, a prospective observational cohort study of 937 term newborns .37 weeks' gestation with birth weights of $2,500 g who were breastfed (BF, n5420, 45%), formula fed (FF, n5396, 42%), or mixed fed (n5121, 13%) were followed for up to 21 days to determine maximal weight loss, timing of maximal weight loss, and time at which birth weight was regained. 2 Maximal weight loss differed significantly by feeding method at the 95th percentile for BF (-11.8%; 95% CI, 11.2-12.9) and FF (-8.4%; CI, 7.8-8.9) as well as the 97.5th percentile for BF (-12.8%; CI, 12.1-13.7) and FF (-9.5%; CI, 8.6-10.9). Weight loss nadir was 2.7 days for both groups. Median recovery of birth weight was 8.3 days for BF (as long as 18.7 days at the 95th percentile) and 6.5 days for FF (as long as 14.5 days at the 95th percentile). Authors recommended evaluation for other etiologies of weight loss if a FF infant had .10% weight loss or failed to regain birth weight by two weeks of life. Biochemical testing for dehydration was recommended for BF or FF infants with .12.5% weight loss or for failure to regain birth weight by three weeks.In 2017, the Academy of Breastfeeding Medicine (ABM) released revised evidence-based guidelines, which recommend supplemental feeding with formula to neonates only in certain situations. 3 Infant indications for supplemental formula feeding included asymptomatic hypoglycemia, significant dehydration, delayed bowel movements, and hyperbilirubinemia. Maternal indications included delayed milk production, lactation failure, breast pathology, chemotherapy, or intolerable pain. The guidelines stated that healthy BF infants may lose 8% to 10% of their birth weight and that as long as an infant urinated and stooled appropriately and the physical examination was normal, the ABM did not recommend formula supplemented feeds.

The authors suggested that this finding was due to selection bias of anticoagulating patients who were at a higher risk of VTE at baseline. Limitations of this study included its retrospective design, the possibility of patient noncompliance with prescribed medications, and including only reported symptomatic VTEs.