Modifying the capecitabine dosing schedule from 14 days on, 7 days off (14/7) to 7 days on, 7 days off (7/7) may enable higher doses and improved antitumor efficacy in colorectal cancer xenografts. Capecitabine 14/7 (267 or 400 mg/kg) and 7/7 (467 or 700 mg/kg) schedules in doublet and triplet combinations with optimally dosed bevacizumab (5 mg/kg) and oxaliplatin (6.7 mg/kg) were studied in female athymic nude mice bearing HT29 colorectal xenografts. Additional studies of suboptimally dosed bevacizumab (2.5 mg/kg) and capecitabine 7/7 (360 mg/kg) were done in a similar Colo205 tumor xenograft model. Monotherapy and combination regimens were administered to groups of 10 animals and compared with vehicle controls. In the HT29 model, tumor growth inhibition and increase in life span (ILS) were significantly greater with capecitabine 7/7 than with 14/7 (P < 0.05).
Levels of some bone turnover markers varied during the menstrual cycle. A statistically significant change in sCTX (9.46%) occurred between the FP and LP of the menstrual cycle.
The sore throat pain model was employed in this randomized, placebo-controlled trial to examine the sensitivity of the model in testing the efficacy of valdecoxib as an acute analgesic drug. Changes were made to the study design by employing a different diagnostic index for tonsillo-pharyngitis, a different rating scale (derived from Lasagna's pain thermometer), and alternative analyses, individual responder rates. Under double-blind conditions, 197 patients with painful pharyngitis were randomly allocated to valdecoxib 20 mg bid (n = 65), valdecoxib 40 mg qd (n = 66), or placebo (n = 66) for 24 hours. The expanded Tonsillo-Pharyngitis Assessment and the Lasagna Pain Scale were validated as sensitive study instruments. Both dosage regimens provided significantly greater pain relief compared with placebo on standard efficacy measures over the 24-hour study (all P < .05). Tests for individual response (eg, percentage of patients with at least moderate relief) confirmed these results, and other response rates identified the high sensitivity of the model itself (eg, only 5% of placebo-treated patients achieved >or=50% of maximum total pain relief over 6 hours). These findings indicate that sore throat is a sensitive model to assess analgesic efficacy.
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