European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Multicenter Study Clinical Trial
Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group.
Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). In this study, GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer (EORTC) phase I/II clinical study of imatinib were examined for mutations of c-KIT/PDGFRA in order to explore whether the mutational status of the tumour predicts the clinical response to therapy. Mutations were screened by denaturing high-pressure liquid chromatography (DHPLC) and characterised by bi-directional DNA sequencing. ⋯ The overall survival and progression-free survival rates for the entire group at 106 weeks were 78.3% and 46.9%, respectively. Based on a Kaplan-Meier analysis, patients with GISTs harbouring c-KIT mutations had longer median survival times and were less likely to progress than the other patients. These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy.
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Randomized Controlled Trial Multicenter Study Clinical Trial
The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials.
In early clinical trials, the NK(1) receptor antagonist, aprepitant (EMEND(R)) was shown to improve the protection provided by the best available therapy (hereafter referred to as 'standard therapy': a 5-HT(3) receptor antagonist and dexamethasone) against chemotherapy-induced nausea and vomiting over multiple cycles of cisplatin-based chemotherapy. To further study the sustainment of antiemetic efficacy of aprepitant plus standard therapy over more than one cycle of chemotherapy, we examined combined data from the multiple cycles extensions of two phase III clinical trials of oral aprepitant plus standard therapy for the prevention of chemotherapy-induced nausea and vomiting. Data were pooled from two multicentre, randomised, double-blind, placebo-controlled studies with identical design and treatment regimens. ⋯ In every cycle, the estimated probabilities (rates) of no emesis and no significant nausea were significantly higher (P<0.006) in the aprepitant group: in the first cycle, rates were 61% in the aprepitant group (N=516) and 46% in the standard therapy group (N=522), and thereafter, rates for the aprepitant regimen remained higher throughout (59% (N=89) versus 40% (N=78) for the standard therapy, by cycle 6). Repeated dosing with aprepitant over multiple cycles was generally well tolerated. Compared with patients who received standard therapy alone (a 5-HT(3) antagonist plus dexamethasone), those who received aprepitant in addition to standard therapy had consistently better antiemetic protection that was well maintained over multiple cycles of highly emetogenic chemotherapy
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Multicenter Study
Going up or coming down? The changing phases of the lung cancer epidemic from 1967 to 1999 in the 15 European Union countries.
Lung cancer, the most common cause of cancer death in the European Union (EU), continues to have an enormous impact on the health experience of the men and women living in the constituent countries. Information on the course of the lung cancer epidemic is essential in order to formulate an effective cancer control policy. This paper examines recent trends in lung cancer mortality rates in men and women in each of the 15 countries, comparing cross-sectional rates of death in younger (aged 30-64 years) and older populations (aged 65 years or over), and the age, period of death, and birth cohort influences in the younger age group. ⋯ In women, recent smoking trends are downwards in Belgium, Denmark, Sweden and the Netherlands, although in Austria and Spain, large increases in smoking prevalence amongst adults are emerging. Unambiguous public health messages must be effectively conveyed to the inhabitants of the EU if the lung cancer epidemic is to be controlled. It is imperative that anti-tobacco strategies urgently target women living in the EU, in order to halt their rapidly increasing risk of lung cancer, and prevent unnecessary, premature deaths among future generations of women.
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Multicenter Study Clinical Trial
Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study.
The aim of this study was to assess the antitumour response and time to progression (TTP) of patients treated with imatinib mesylate (Glivec, Gleevec, formerly STI-571) who had advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS). Patients with measurable lesions and adequate organ function were entered. They were treated with imatinib mesylate at the dose of 400 mg twice daily (bid). ⋯ The median time to progression in this subgroup was only 58 days. Imatinib mesylate is well tolerated at a dose of 400 mg bid. This dose is active in patients with KIT-positive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Functional relevance of antiemetic control. Experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant.
Little information exists on the functional impact of effective antiemetic protection. In the present study, the Functional Living Index-Emesis (FLIE), was used to assess patient-reported impact of chemotherapy-induced nausea and vomiting (CINV) after administration of a new NK-1 receptor antagonist (aprepitant). ⋯ Compared with standard therapy, significantly more patients treated with the high dose aprepitant regimen achieved a Complete Response (71 vs 44%, P<0.001) and also reported no impact on daily life as indicated by the FLIE total score (84 vs 66%, P<0.01). Use of the FLIE demonstrated that improved control of emesis was highly effective in reducing the impact of CINV on patients' daily lives.