OS, PFS, QOL, and RR were comparable between arms. Adding E to G did not increase hematologic toxicities. GE does not warrant further investigation in unselected pancreatic cancer patients.

Palliation is the primary goal in metastatic breast cancer (MBC), and safe, efficacious, new single-agent options are needed. Pemetrexed, an antifolate, inhibits several folate-dependent enzymes involved in purine biosynthesis. The primary goal of this study was to determine the objective response rate in patients with advanced or MBC given pemetrexed as a first-line, dose-dense, every 2-week chemotherapy. Women with HER2-negative advanced or MBC, without prior cytotoxic treatment for this stage of disease, were treated with intravenous pemetrexed 600 mg/m² on Day 1 of each 14-day cycle. Standard dexamethasone, folic acid, and vitamin B(12) premedications were given. 37 patients enrolled; 36 received ≥ 1 dose of pemetrexed and 35 were evaluable for response. Median age of patients was 61.4 years, 76% were hormone receptor positive (ER+ and/or PR+). Prior treatment included adjuvant chemotherapy (57%) and/or endocrine (65%). Patients received a median of 6 cycles of pemetrexed (range, 1-21). Based on 35 evaluable patients, the overall response rate (ORR) was 26% (1 CR and 8 PR), and the clinical benefit rate (CR+ PR+ stable disease [SD] ≥ 6 months) was 40%. Median progression-free survival (PFS) was 4.1 months (range, <1-22.4). Median overall survival (OS) was 18.9 months (range, <1-27.7). Grades 3-4 treatment-related toxicities included: neutropenia (36%), leukopenia (17%), fatigue (14%), and anemia (14%). Grade 1/2 alopecia was seen in 8% of patients. This phase II study of dose-dense, single-agent pemetrexed showed moderate activity in the first-line setting with acceptable toxicity and no significant alopecia.

No abstract

SummaryThe effect of pharmacologic doses of adrenal corticosteroids upon plasma fibrinogen level, incorporation of 75Se-Methionine (75SeM) into fibrinogen, and disappearance of plasma 125I-fibrinogen was evaluated in rabbits. Single 25 mg doses of hydrocortisone or cortisone transiently increased both 75SeM incorporation into fibrinogen and plasma fibrinogen levels, but 1 to 5 mg doses of hydrocortisone had no significant effect upon plasma fibrinogen levels. Repeated daily injections of 25 mg of hydrocortisone did not increase plasma fibrinogen levels progressively. Two doses of 25 mg of hydrocortisone, given 24 hr apart, failed to alter the rate of disappearance of plasma 125I-fibrinogen radioactivity, i.e., plasma fibrinogen catabolism. Intramuscular injection of 2.5 ml of propylene glycol solvent caused a prolonged rise in plasma fibrinogen level, whereas injection of 25 mg of corticosterone dissolved in propylene glycol resulted in an attenuated and transient rise in plasma fibrinogen level. Apparently, the presence or absence of a coexistent inflammatory stimulus determines the overall effect of large pharmacologic doses of corticosteroids upon fibrinogen metabolism in the rabbit. In the presence of inflammation, corticosteroids decrease synthesis with a resultant fall in plasma fibrinogen level; in the absence of inflammation, corticosteroids may increase synthesis transiently with a resultant slight increase in plasma fibrinogen level.