6 results on '"Zdenkowski, Nicholas"'
Search Results
2. Oncology patients' and oncology nurses' views on palliative chemotherapy: A cross-sectional comparison.
- Author
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Shepherd, Jan, Waller, Amy, Sanson-Fisher, Rob, Zdenkowski, Nicholas, Douglas, Charles, and Clark, Katherine
- Published
- 2021
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3. Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio.
- Author
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Lee, Clara Inkyung, Low, Siew Kee, Maldonado, Ricardo, Fox, Peter, Balakrishnar, Bavanthi, Coulter, Sally, de Bruijn, Peter, Koolen, Stijn L.W., Gao, Bo, Lynch, Jodi, Zdenkowski, Nicholas, Hui, Rina, Liddle, Christopher, Mathijssen, Ron H.J., Wilcken, Nicholas, Wong, Mark, and Gurney, Howard
- Subjects
TAMOXIFEN ,FORECASTING ,CLASSIFICATION - Abstract
CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome. A target NDMT/E ratio was defined as associated with an E level of 15 nM in the 161 patient Test cohort of tamoxifen-treated patients, dichotomizing them into 'Normal' (NM) and 'Slow' (SM) CYP2D6 metabolizer groups. This ratio was then tested on a validation cohort of 52 patients. Patients were phenotyped based on the standard method (ultrarapid/extensive, intermediate or poor metabolizers; UM/EM, IM, PM) or a simplified system based on whether any variant allele (V) vs wildtype (wt) was present (wt/wt, wt/V, V/V). Comprehensive CYP2D6 genotyping was undertaken on germline DNA. A target NDMT/E ratio of 35 correlated with the 15 nM E level, dichotomizing patients into NM (<35; N = 117) and SM (>35; N = 44) groups. The ratio was independently validated by a validation cohort. The simplified system was better in predicting patients without slow metabolism, with specificity and sensitivity of 96% and 44% respectively, compared with the standard method - sensitivity 81% and specificity 83%. The simplified classification system based on whether any variant was present better identified patients who were truly not CYP2D6 slow metabolizers more accurately than the current system. However, as CYP2D6 genotype is not the only determinant of endoxifen level, we recommend that direct measurement of endoxifen should also be considered. • We used a ratio of two tamoxifen metabolites to categorize CYP2D6 metabolizer groups. • We developed a simplified system to identify slow metabolizers based on genotype. • The simplified system was more accurate than the standard complex system. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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4. Patient-reported outcomes with neoadjuvant vs adjuvant systemic therapy for operable breast cancer.
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Zdenkowski, Nicholas, Butow, Phyllis, Spillane, Andrew, Douglas, Charles, Snook, Kylie, Jones, Mark, Oldmeadow, Christopher, Fewster, Sheryl, Beckmore, Corinna, and Boyle, Frances M.
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BREAST cancer ,THERAPEUTICS ,CANCER ,SATISFACTION ,LONGITUDINAL method ,FEAR - Abstract
Neoadjuvant systemic therapy (NAST) is used for large operable or highly proliferative breast cancers. It is not known whether psychological outcomes differ according to the treatment sequence (chemotherapy or surgery first) or tumour response. This was a planned analysis of a multi-institutional single arm longitudinal study of patients considering NAST for operable breast cancer. Participants completed patient reported outcome questionnaires before and after the decision about NAST, between chemotherapy and surgery, and 12 months after diagnosis. Fifty-nine women enrolled. Fourteen of 51 (28%) who received NAST experienced pathological complete response (pCR). Patients who had surgery first (n = 7) had higher baseline anxiety, and a greater decrease in anxiety at 12 months follow up, compared with patients who received NAST (n = 50) (a decrease from baseline of 34 pts vs 17 points; p = 0.033). Distress declined at a similar rate in surgery first and NAST groups. Mean satisfaction with decision score post-decision was significantly lower in the adjuvant group compared with NAST (22 vs 26, p = 0.02). No differences were seen between patients with pCR vs residual cancer in: distress, anxiety, satisfaction with decision, fear of progression, and decision regret. Most patients in this study proceeded with NAST when their surgeon offered it as an option. This exploratory analysis suggests that patients who chose surgery first tended to be more anxious, and had lower satisfaction with their decision, than those who had NAST. In patients who had NAST, lack of pCR does not appear to correlate with adverse psychological outcomes. • Psychological outcomes from neoadjuvant therapy for breast cancer are unknown. • We questioned 59 women about anxiety, distress, and fear of progression or recurrence. • Outcomes were compared according to response to chemotherapy and scheduling. • Anxiety and distress declined over time. • Fear of progression or recurrence were no different in responders or non-responders. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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5. Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial.
- Author
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Cuzick, Jack, Chu, Kim, Keevil, Brian, Brentnall, Adam R, Howell, Anthony, Zdenkowski, Nicholas, Bonanni, Bernardo, Loibl, Sibylle, Holli, Kaija, Evans, D Gareth, Cummings, Steve, and Dowsett, Mitch
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BREAST cancer , *HORMONE therapy , *ANASTROZOLE , *ESTRADIOL , *CANCER cell growth , *CASE-control method - Abstract
An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40–70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol–SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone–SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 – the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106–156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol–SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone–SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol–SHBG ratio, but not in quartile 1 (0·18 [–0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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6. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study.
- Author
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Mayer, Erica L, Dueck, Amylou C, Martin, Miguel, Rubovszky, Gabor, Burstein, Harold J, Bellet-Ezquerra, Meritxell, Miller, Kathy D, Zdenkowski, Nicholas, Winer, Eric P, Pfeiler, Georg, Goetz, Matthew, Ruiz-Borrego, Manuel, Anderson, Daniel, Nowecki, Zbigniew, Loibl, Sibylle, Moulder, Stacy, Ring, Alistair, Fitzal, Florian, Traina, Tiffany, and Chan, Arlene
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HORMONE receptor positive breast cancer , *HORMONE therapy , *BREAST cancer , *METASTATIC breast cancer , *PROGRESSION-free survival , *LUTEINIZING hormone , *PYRIDINE , *PROTEINS , *RESEARCH , *HETEROCYCLIC compounds , *RESEARCH methodology , *ANTINEOPLASTIC agents , *PROGNOSIS , *CELL receptors , *EVALUATION research , *MEDICAL cooperation , *COMPARATIVE studies , *AROMATASE inhibitors , *TAMOXIFEN , *BREAST tumors , *PROPORTIONAL hazards models - Abstract
Background: Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer.Methods: PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II-III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1-21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30).Findings: Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9-29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2-90·6) for palbociclib plus endocrine therapy and 88·5% (85·8-90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76-1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3-4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths.Interpretation: At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing.Funding: Pfizer. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
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