Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Jun 2005
Gefitinib (ZD1839, Iressa) in non-small-cell lung cancer: a review of clinical trials from a daily practice perspective.
Gefitinib (ZD1839) is the most widely studied targeting agent in the area of non-small-cell lung cancer (NSCLC). Gefitinib is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor. In order to assess the role of gefitinib in the management of NSCLC patients, we systematically reviewed published clinical trials from a daily practice perspective. ⋯ Furthermore, we also reviewed the results of studies interested in the characterization of predictive clinical or biological markers for response to gefitinib and discussed the results obtained with other EGFR inhibitors. The efficacy of gefitinib in the first-line setting of each stage of NSCLC has to be further studied through clinical trials. Furthermore, translational studies characterizing the molecular features involved in the response to anti-EGFR-targeted therapies are needed.
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Fundam Clin Pharmacol · Dec 2004
Randomized Controlled Trial Clinical TrialEffect of preoperative oral sustained-release morphine sulfate on postoperative morphine requirements in elective spine surgery.
Sustained-release morphine sulfate (SRMS) is a painkiller used in oncology. The purpose of our study was to assess its efficacy on postoperative morphine requirements in elective spine surgery. This was a placebo-controlled, randomized, double-blind study. ⋯ Morphine consumption through PCA during the 24 h following extubation was also significantly lower in the SRMS group (15.9 +/- 12.7 mg) compared with the placebo group (23.8 +/- 10.9 mg, P = 0.032). Vigilance, nausea and respiratory rate 3 and 6 h after extubation were similar in the two groups. A preoperative oral administration of SRMS (30 mg) induces a 33% reduction of postoperative morphine requirements in patients scheduled for spine surgery without inducing side effects.
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This paper reviews state-of-art statistical designs for dose-escalation procedures in first-into-man studies. The main focus will be on studies in oncology, as most statistical procedures for phase I trials have been proposed in this context. ⋯ The number of dose levels and cohort sizes used in early phase trials are considered. Finally, this paper raises some practical issues for dose-escalation procedures.
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Fundam Clin Pharmacol · Jun 2004
Comparative Study Clinical TrialBlood pressure and heart rate variability changes during cardiac surgery with cardiopulmonary bypass.
This study investigated patients undergoing elective cardiac surgery to evaluate the effects of cardiopulmonary bypass (CPB) on the spontaneous variability of mean arterial pressure (MAP) and heart rate (HR). Forty-one adult patients receiving different cardiovascular system drugs were included in the study. Patients were divided into three groups: no preoperative pharmacological cardiovascular treatment (n = 12), beta-blocker (BB) (n = 13), and angiotensin-converting enzyme inhibition (ACEI) (n = 16). ⋯ LF spectral power of HR showed a large decrease after CPB in ACEI group (-89%). This study showed that MAP variability did not change during CPB in patients with no preoperative pharmacological cardiovascular treatment, suggesting an unaltered vascular control of MAP. Moreover, the change in LF spectral power of MAP in ACEI and BB groups, suggests that both the renin-angiotensin and sympathetic systems participate to the genesis of LF variability of MAP.
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Fundam Clin Pharmacol · Jun 2004
ReviewAssessment of patient-reported outcomes in clinical trials: the example of health-related quality of life.
As the patient is the primary recipient of treatment, there is a need to recognize and value the patient's perception of change in response to treatment in clinical trials. A new outcomes classification, patient-reported outcomes (PROs), has been proposed by regulators. The PROs are used as an umbrella term and include, for example measures of subjective symptoms, health-related quality of life (HRQL) and treatment satisfaction. ⋯ However, important issues of particular relevance to PRO assessments, such as missing values, multiple outcomes, and the statistical analysis, require careful attention. The thinking and planning involved in developing the PRO component of the clinical trial need to be articulated. Successful evaluation of PROs in clinical trials relies on careful planning provided the treatment shows sufficient effectiveness.