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- Baselga, J, et al.
(författare)
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Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types
- 2002
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 20:21, s. 4292-4302
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
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| 2. |
- Pavan, J, et al.
(författare)
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Lifetime measurements and terminating structures in Nb-87
- 2003
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 67:3: 034316
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Tidskriftsartikel (refereegranskat)abstract
- Two experiments have been performed using the Ni-58(S-32,3p) reaction at 135 MeV with Gammasphere and the Microball to study the high-spin structure of the transitional nucleus Nb-87. The first experiment using a thin target provided a considerable extension and refinement of the level scheme, as well as firm spin assignments from directional correlation of oriented nuclei. Sub-picosecond lifetimes were measured in the second backed-target experiment using the Doppler-shift attenuation method. The lifetimes imply a rather modest average deformation of beta(2)similar to0.1, but with considerable variation from state to state. Strong alternations were observed in the B(M1) strengths of transitions between some pairs of bands. The experimental results were compared with calculations performed within the cranked Nilsson-Strutinsky approach. The calculations generally reproduce the irregularities in the structure of the yrast lines and plunging transition quadrupole moments Q(t) within the bands explaining them as reflections of configuration changes and an approach of band termination, respectively.
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| 3. |
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| 4. |
- Cardona, R., et al.
(författare)
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High-spin structure of normal-deformed bands in 84Zr
- 2003
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Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 68, s. 1-024303
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Tidskriftsartikel (refereegranskat)abstract
- The reaction 58Ni(32S, α2p) at E lab= 135 MeV was used to populate high-spin states in 84Zr. The complete GAMMASPHERE and MICROBALL arrays were used to obtain clean γ- γ- γ line shapes to be analyzed by the Doppler shift attenuation method and to determine 27 lifetimes in the ground-state band and in two excited bands. Side-feeding times were also measured by comparing the line shapes gated with transitions above and below the state under study. The deduced electric quadrupole moments for the ground-state band are consistent with a very slow reduction with frequency with values ranging between 2.4(3) and 2.0(1)e b. The negative-parity bands feature also an approximate constancy of quadrupole moment with values similar to those in the ground-state band. Cranking calculations agree with this behavior in both parity bands and suggest an interpretation of the upper states in the ground-state band as part of a very slowly terminating band. Shell-dependent cranked Nilsson calculations explain a fourth γ cascade as pertaining to a noncollective structure terminating at I = 20+.
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| 7. |
- Klump, KL, et al.
(författare)
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Personality characteristics of women before and after recovery from an eating disorder
- 2004
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Ingår i: Psychological medicine. - : Cambridge University Press (CUP). - 0033-2917 .- 1469-8978. ; 34:8, s. 1407-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies of personality characteristics in women with eating disorders primarily have focused on women who are acutely ill. This study compares personality characteristics among women who are ill with eating disorders, recovered from eating disorders, and those without eating or other Axis I disorder pathology.Method. Female participants were assessed for personality characteristics using the Temperament and Character Inventory (TCI): 122 with anorexia nervosa (AN; 77 ill, 45 recovered), 279 with bulimia nervosa (BN; 194 ill, 85 recovered), 267 with lifetime histories of both anorexia and bulimia nervosa (AN+BN; 194 ill, 73 recovered), 63 with eating disorder not otherwise specified (EDNOS; 31 ill, 32 recovered), and 507 without eating or Axis I disorder pathology.Results. Women ill with all types of eating disorders exhibited several TCI score differences from control women, particularly in the areas of novelty-seeking, harm avoidance, self-directedness, and cooperativeness. Interestingly, women recovered from eating disorders reported higher levels of harm avoidance and lower self-directedness and cooperativeness scores than did normal control women.Conclusions. Women with eating disorders in both the ill and recovered state show higher levels of harm avoidance and lower self-directedness and cooperativeness scores than normal control women. Although findings suggest that disturbances may be trait-related and contribute to the disorders' pathogenesis, additional research with more representative community controls, rather than our pre-screened, normal controls, is needed to confirm these impressions.
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| 8. |
- LoRusso, Patricia M, et al.
(författare)
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Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors
- 2003
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 9:6, s. 2040-2048
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The feasibility and utility of assessing quality of life (QoL) and disease-related symptoms in patients with advanced cancer have been evaluated in two Phase I clinical trials of p.o. administered ZD1839 ('Iressa'), an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced cancer. EXPERIMENTAL DESIGN: Functional Assessment of Cancer Therapy (FACT) questionnaires, including disease-specific subscales for lung, head and neck, colorectal, prostate, and ovarian cancer, were completed by patients in two open-label, Phase I, escalating multiple-dose safety and tolerability trials. RESULTS: In 157 patients, 92% of whom had received prior therapy, compliance in returning FACT questionnaires was 87% (European/Australian trial) and 57% (United States trial). This did not appear to be influenced by dose level or tumor type. For patients with colorectal, prostate, or ovarian cancer, median QoL [FACT and Trial Outcome Index (TOI)] scores deteriorated over time. In contrast, for patients with non-small cell lung cancer (NSCLC) or head and neck cancer, median FACT and TOI scores did not deteriorate significantly, and in the United States trial, head and neck cancer scores improved significantly over time. In patients with NSCLC, symptom-related scores measured by the Lung Cancer Subscale of FACT-L appeared sensitive to clinical change. CONCLUSIONS: QoL (FACT-L) questionnaires were used successfully in the Phase I clinical trials of ZD1839. They appeared to be a sensitive tool to monitor clinical changes for the five tumor types in these trials and showed that ZD1839 has the potential to improve patients' QoL.
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| 9. |
- Wiedeking, M., et al.
(författare)
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Transition strengths and band terminations in 86Zr
- 2003
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Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 67, s. 1-034320
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Tidskriftsartikel (refereegranskat)abstract
- High angular momentum states in 86Zr were populated through the 58Ni(32S,4p) reaction at 135 MeV using the 88-In. Cyclotron at Lawrence Berkeley National Laboratory. Recoiling 86Zr nuclei were stopped in a thick Ta backing. Prompt multi-γ coincidences with evaporated charged particles were detected using the full array of GAMMASPHERE and the MICROBALL. Mean lifetimes of 36 levels in 86Zr were measured using the Doppler-shift attenuation method. Transition quadrupole moments Qt were found in the range of about 0.3-1.5 e b in the positive-parity bands. The negative-parity bands show Qt values from about 0.25 to 1.2 e b. In the yrast positive-parity band, a sharp drop in collectivity approaching the 30+ state supports the interpretation of band termination in this configuration. Decreasing Qt values approaching the 24+ and 27- states also provide an indication of terminating structures.
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| 10. |
- Woodside, DB, et al.
(författare)
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Personality in men with eating disorders
- 2004
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Ingår i: Journal of psychosomatic research. - : Elsevier BV. - 0022-3999. ; 57:3, s. 273-278
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Tidskriftsartikel (refereegranskat)
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