Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A multicenter, open labeled, randomized early Phase II study for CGS 20267 was conducted at the doses 0.5 mg once daily and 1.0 mg once daily in postmenopausal women with advanced breast cancer. Sixty-four patients were randomly assigned to the doses of either 0.5 mg once daily (n = 33) or 1.0 mg once daily (n = 31). Thirty-one patients were eligible for 0.5 mg group, and 29 for 1.0 mg group. A total of 57 patients (30 in the 0.5 mg group and 27 in the 1.0 mg group) were eligible for the evaluation of efficacy. There were 3 CR, 5 PR, 5 stable disease (SD: NC lasting over 24 weeks), 7 NC and 10 PD in the 0.5 mg group. The objective response rate (ORR) was 26.7%. There were 4 CR, 7 PR, 8 SD, 3 NC and 5 PD in the 1.0 mg group. The ORR was 40.7%. A total of 57 patients (29 in the 0.5 mg group and 28 in the 1.0 mg group) were eligible for safety evaluation. Adverse clinical events related to CGS 20267 in the 0.5 mg group were headache, nausea, cold sweat, sleepiness and muscle ache in the lower extremities (2 patients, incidence rate 6.9%) whereas those in the 1.0 mg group were generalized itching and generalized hot feeling (2 patients, incidence rate 7.1%). All of the adverse events were grade 1 except the generalized itching which was grade 2. CGS 20267-related abnormalities in the laboratory tests for the 0.5 mg group were a decrease in WBC, and increases in GOT, GPT, LDH and gamma-GTP (5 patients, 14.3%) whereas those in the 1.0 mg group were increases in GPT, gamma-GTP, alkaline phosphatase, and total bilirubin (1 patient, 3.6%). The increases in GOT and GPT were grade 2, but others were grade 1. The data show both CGS 20267 0.5 mg once daily and 1.0 mg once daily to be effective and tolerable in the treatment of postmenopausal women with advanced breast cancer.
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PMID:[CGS 20267 (Letrozole), a new aromatase inhibitor: early phase II study for postmenopausal women with advanced breast cancer]. 1197 39

A multiple-dose administration study of exemestane (0.5-50 mg/day after breakfast for 7 days) was conducted in 32 normal healthy postmenopausal Japanese women using a single-blind, 3-step dose-titration method in order to investigate the safety, effect on serum concentration, amount of urinary estrogen excretion, and pharmacokinetics of the drug. Subjective/objective symptoms, in which a causal relationship with exemestane administration could not be excluded, were as follows: headache (8 cases: 1 each in the 0.5 and 25 mg groups, 2 in the 10 mg group and 4 in the 50 mg group), dizziness (2 cases: 1 each in the 0.5 and 25 mg groups), and fever (1 in the 25 mg group), all of which were mild and disappeared without treatment. The only abnormal laboratory findings were a mild increase in levels of GOT and GPT in 1 case and in the number of basophils in another case. There were no notable abnormal findings in vital signs, body weight or EKG. A dose-dependent decrease in serum estrogen level was observed between doses of 0.5 mg and 25 mg. The decrease was maximal at 25 mg, at which serum estrogen concentrations decreased to 14-27% of those observed at day 0. This decrease was maintained for one week, returning to baseline levels 2 weeks after the completion of drug administration. A similar result was also observed in the suppression of 24-hour urinary estrogen excretion. Exemestane was absorbed immediately after initial administration, reaching Cmax 0.9-2.6 hours post-administration. This was followed by a rapid decrease over the next 4-8 hours followed by a gradual decrease Cmax reached normal steady state values on day 5. Cmax and AUC0-24 values taken between administration of the first and final doses increased proportionally in a dose-dependent manner, suggesting that exemestane has a linear pharmacokinetic profile. Furthermore, results of the comparison of the trough concentrations of the initial dose with those of the final dose suggested no accumulative effects of the study drug.
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PMID:[Phase I multiple-dose administration study of exemestane in postmenopausal women]. 1214

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.
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PMID:[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer]. 1214 1

We examined the clinical symptoms and laboratory findings of 21 children with aseptic meningitis caused by echovirus 13 during the summer of 2002. All patients (mean age: 8.3 years) complained of fever and headache. Some had mild vomiting and some had severe vomiting of 4 times or more. In the early stage of the disease, the mean count of WBC was 8,283/microliter, mean level of CRP was 0.8 mg/dl, and there were no abnormalities in levels of GOT, GPT, or LDH. The levels of protein and sugar, in cerebrospinal fluid showed no abnormalities, and mean total cell count was 560/microliter. The mean number of polynuclear cells was 357/microliter, and of mononuclear cells was 203/microliter, showing polynuclear cell predominance. In the recovery period, the tendency to polynuclear cell predominance in the early stage of the disease shifted to mononuclear predominance. One of the 21 patients exhibited multinucleated cell predominance in the cerebrospinal fluid, a high CRP value of 6.2 mg/dl, as well as symptoms of restlessness including numbness of the limbs, hyperpnea, and excitation, needed careful diagnosis as aseptic meningitis. Almost all of the patients were mild cases, and no large differences were seen with the clinical and laboratory findings in previous reports of echovirus aseptic meningitis.
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PMID:[Clinical analysis of aseptic meningitis caused by echovirus 13]. 1457 43


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