\n\nThis was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0-2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m(2) intravenously (IV) and irinotecan 50 mg/m(2) IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall
survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning.\n\nA total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age IAP inhibitor was 57.8 years (31-79 years) and 74% were male. Two patients had a complete response, with nine patients achieving
a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary MK-8776 mw to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy.\n\nOxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens.”
“A novel linear multifunctional polyethylene glycol (PEG)-dexamethasone (Dex) conjugate (click PEG-Dex) was synthesized using, facile Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a click reaction). Des was conjugated to the click PEG via an acid-labile hydrazorie bond to allow the drug release in a pathophysiological environment. To evaluate click
PEG’s potential as a versatile drug delivery platform, the click PEG-Dex conjugates were tested in an adjuvant-induced arthritis (AA) rat model. In vivo optical imaging data confirmed the arthrotropism of the ALK targets conjugates in the arthritic rots. A long-term treatment study revealed that a single click PEG-Dex conjugate administration provided sustained (> 15 days) amelioration of ankle joint inflammation to the AA rats. Treatment with an equivalent dose of dexmethasone phosphate sodium (free Dex) only provided temporal resolution of the arthritis, which recurred upon treatment-withdrawal. Further histological and bone mineral density comparison between the ankle joints from both click PEG-Dex and free Dux treatment groups confirmed the superior anti-inflammatory and disease modifying effects of the novel polymer -drug conjugates.