Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma

Background Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]). Methods The clinical information was collected by a retrospective medical record review under an Institutional Review Board-approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined. Results Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed. Conclusion This suggests that the combination of AMG-479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC

Sulfated zirconia as a robust superacid catalyst for multiproduct fatty acid esterification

Sulfated zirconia catalysts obtained by employing chlorosulfuric acid show significantly higher activity in the esterification of fatty acids with different alcohols compared with catalysts made using sulfuric acid. The superior performance results from higher sulfur content, larger pores and stronger acid sites. These catalysts are robust and do not leach out sulfonic groups. Catalyst performance depends strongly on the sulfation reagent and the calcination conditions of the intermediate zirconium hydroxide. A series of kinetic experiments was carried out with lauric acid and various alcohols (methanol, 2-ethylhexanol, propanols and butanols). The new catalysts are ca. five times faster when using primary alcohols independent of the alcohol chain length. When using secondary and tertiary alcohols the reaction rate drops considerably. This is explained by a linear free energy relationship of substituent reactivity. The kinetic investigation shows that chlorosulfated zirconia is suitable as a multiproduct catalyst for manufacturing fatty esters, by employing a catalytic reactive distillation process

Mepolizumab

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The May 2016 monograph topics are sugammadex, lesinurad, selexipag, sebelipase alfa, and alectinib. The Safey MUE is on sugammadex

Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials

Background: We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials. Methods: Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum. All statistical tests were 2-sided. Results: Older adults comprised 16.4% of patients on first-line trials (870 total older adults aged >70 years; 4419 total younger adults less than 70 years, on first-line trials). Older adults and those with Eastern Cooperative Oncology Group Performance Status >0 were less likely to receive second-line therapy than younger adults. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariable analysis (odds ratio ¼ 1.11, 95% confidence interval ¼ 1.02 to 1.21, P ¼ .01). Older and younger adults enrolled in second-line trials experienced similar median TTP and median OS (median TTP ¼ 5.1 vs 5.2 months, respectively; median OS ¼ 11.6 vs 12.4 months, respectively). Conclusions: Older adults were less likely to receive second-line therapy for metastatic colorectal cancer, though we did not observe a statistical difference in survival outcomes vs younger adults following second-line therapy. Further study should examine factors affecting decisions to treat older adults with second-line therapy. Inclusion of geriatric assessment may provide better criteria regarding the risks and benefits of second-line therapy.Nadine J. McCleary, MD, MPH, William S. Harmsen, MS, Ellana Haakenstad, MPH, James M. Cleary, MD, PhD, Jeffrey A. Meyerhardt, MD, MPH, FASCO, John Zalcberg, PhD, MBBS, Richard Adams, MD, Axel Grothey, MD, Alberto F. Sobrero, MD, Eric Van Cutsem, MD, PhD, Richard M. Goldberg, MD, FASCO, Marc Peeters, MD, PhD, Josep Tabernero, MD, Matt Seymour, MD, Leonard B. Saltz, MD, Bruce J Giantonio, MD, Dirk Arnold, MD, Mace L. Rothenberg, MD, Miriam Koopman, MD, Hans-Joachim Schmoll, MD, Henry C. Pitot, MD, Paulo M. Hoff, MD, Niall Tebbutt, MD, Gianluca Masi, MD, John Souglakos, MD, PhD, Carsten Bokemeyer, MD, Volker Heinemann, MD, Takayuki Yoshino, MD, PhD, Benoist Chibaudel, MD, Aimery deGramont, MD, Qian Shi, PhD, Stuart M. Lichtman, M