Ian F Tannock

University Health Network, Toronto, Ontario, Canada

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Publications (320)3016.84 Total impact

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    ABSTRACT: Drugs used to treat cancer have neurotoxic effects that often produce memory loss and related cognitive deficits. In a test of the hypothesis that chemotherapy-induced cognitive impairment is related to a loss of inhibitory control, rats injected with a combination of methotrexate+5-fluouracil or equal volumes of saline, were administered a retroactive interference task in which memory for a learned discrimination problem was tested under conditions of high- and low-interference. The drugs had no effect on original learning or on re-learning the discrimination response when there was little interference, but the chemotherapy group was severely impaired in the hippocampus-sensitive, high-interference memory test. The impaired performance correlated significantly with reduced neurogenesis in the hippocampus. The failure to suppress interfering influences is consistent with a breakdown in pattern separation, a process that distinguishes and separates overlapping neural representations of experiences that have a high degree of similarity. Copyright © 2014. Published by Elsevier B.V.
    Behavioural Brain Research 12/2014; · 3.39 Impact Factor
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    ABSTRACT: The neutrophil to lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy. Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets respectively. Associations of dNLR and duration of initial ADT with OS were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT. In the training set both dNLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death (HR=1.29;95%CI: 1.11-1.50, P<0.001 and HR=1.41; 95%CI: 1.21-1.64, P<0.001 respectively) after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline. In the validation set, dNLR remained an independent prognostic factor for OS (HR=1.43; 95%CI: 1.20-1.70, P<0.001), whereas duration of initial ADT was not (HR=1.16; 95%CI: 0.97-1.37, P=0.10). In subgroup analyses of the TAX327 study, docetaxel improved OS irrespective of dNLR and duration of initial ADT. The dNLR was prognostic for OS in men with mCRPC receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials and could be incorporated into prognostic nomograms. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 12/2014; · 6.58 Impact Factor
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    ABSTRACT: "Waterfall plots" are used to describe changes in tumor size observed in clinical studies. Here we assess criteria for generation of waterfall plots and the impact of measurement error in generating them.
    JNCI Journal of the National Cancer Institute 12/2014; 106(12). · 15.16 Impact Factor
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    ABSTRACT: We aimed to assess the impact of spin (ie, reporting to convince readers that the beneficial effect of the experimental treatment is greater than shown by the results) on the interpretation of results of abstracts of randomized controlled trials (RCTs) in the field of cancer. We performed a two-arm, parallel-group RCT. We selected a sample of published RCTs with statistically nonsignificant primary outcome and with spin in the abstract conclusion. Two versions of these abstracts were used-the original with spin and a rewritten version without spin. Participants were clinician corresponding authors of articles reporting RCTs, investigators of trials, and reviewers of French national grants. The primary outcome was clinicians' interpretation of the beneficial effect of the experimental treatment (0 to 10 scale). Participants were blinded to study hypothesis. Three hundred clinicians were randomly assigned using a Web-based system; 150 clinicians assessed an abstract with spin and 150 assessed an abstract without spin. For abstracts with spin, the experimental treatment was rated as being more beneficial (mean difference, 0.71; 95% CI, 0.07 to 1.35; P = .030), the trial was rated as being less rigorous (mean difference, -0.59; 95% CI, -1.13 to 0.05; P = .034), and clinicians were more interested in reading the full-text article (mean difference, 0.77; 95% CI, 0.08 to 1.47; P = .029). There was no statistically significant difference in the clinicians' rating of the importance of the study or the need to run another trial. Spin in abstracts can have an impact on clinicians' interpretation of the trial results. © 2014 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 11/2014; · 17.88 Impact Factor
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    ABSTRACT: Objective To assess the efficacy and toxicity of abiraterone and docetaxel in men with metastatic castration-resistant prostate cancer (mCRPC) of age > 80 compared to younger men. Methods Retrospective chart review of 116 men treated with abiraterone and 378 men treated with docetaxel at Princess Margaret Cancer Centre. Categorical outcome measures including PSA response rate (PSA-RR) and incidence of toxic side-effects were compared using Fisher's exact test. Overall survival (OS) and biochemical progression free survival (bPFS) were analyzed using the Kaplan–Meier method and log-rank tests. Results Thirty-four (29%) and 50 (13%) of the men treated with abiraterone or docetaxel, respectively, were octogenarians. For abiraterone there were no significant differences in PSA-RR (42% vs. 39%), bPFS (4.7 vs. 4.4 months) or OS (14.0 vs 20.7 months) between octogenarians and younger men, respectively. Toxicity was mild with no significant differences between age groups. For men treated with docetaxel PSA-RR and OS did not differ between age groups (40% vs. 45% and 12.0 vs. 14.1 months, respectively). However, rates of febrile neutropenia were 16% and 7% for octogenarians and younger men, respectively (p = 0.048). This difference was observed despite greater use of lower dose intensity and weekly docetaxel in the elderly cohort, with 20% of them receiving lower than standard dose during their first cycle compared to 7% of younger men (p = 0.004). Conclusions Treatment outcome on abiraterone and docetaxel did not differ in patients over and under the age of 80, but febrile neutropenia was more common in octogenarians treated with docetaxel despite lower dose intensity.
    Journal of Geriatric Oncology 10/2014; · 1.12 Impact Factor
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    ABSTRACT: There are increasing reports of rare but serious toxicities caused by new anticancer drugs, and there are costs associated with their management.
    Journal of Clinical Oncology 09/2014; · 17.88 Impact Factor
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    ABSTRACT: Background In preclinical models, the proton pump inhibitor pantoprazole enhances the antitumor activity of chemotherapeutic agents by improving drug distribution and by inhibiting autophagy. Methods Patients with advanced solid tumors (n = 24) received doxorubicin 60 mg/m(2) and escalating doses of pantoprazole (80, 160, 240 and 360 mg) administered intravenously prior to doxorubicin. Blood samples were collected for pharmacokinetic studies. An optional biopsy was performed to evaluate doxorubicin concentration and pharmacodynamic markers of drug activity. Results Twenty-four patients participated in the study (17 in the dose escalation phase and 7 in the dose expansion). Three patients experienced a dose limiting toxicity (grade 3 fatigue in the three cases), one patient at dose level 3 (pantoprazole 240 mg) and two patients at dose level 4 (pantoprazole 360 mg). Dose level 4 was considered to exceed the maximum tolerated dose. The recommended phase II dose was pantoprazole 240 mg and doxorubicin 60 mg/m(2). The most commonly observed toxicities included fatigue, neutropenia and leukopenia. Two patients achieved a confirmed partial response. Median maximum serum concentration of pantoprazole was 84.3 μM at 1-2 h after injection of pantoprazole 240 mg. No drug-drug interaction was observed. A single on-treatment tumor biopsy showed a sharply decreasing gradient in doxorubicin concentration and associated activity markers with increasing distance from tumor blood vessels. Conclusion Administration of high doses of pantoprazole in combination with doxorubicin is feasible. The recommended phase II dose of pantoprazole, 240 mg, will be evaluated in combination with docetaxel as first line in patients with castration-resistant prostate cancer.
    Investigational New Drugs 09/2014; · 3.50 Impact Factor
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    ABSTRACT: Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC).
    Annals of Oncology 09/2014; · 6.58 Impact Factor
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    ABSTRACT: Introduction Abiraterone (AA) is a CYP17 inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). Data suggest similar pharmacokinetics of 250–500 mg of AA with high-fat meals (‘low-dose’) and 1000 mg in the fasting state (‘full-dose’). Ketoconazole (KT) is a less potent CYP17 inhibitor previously widely used in mCRPC. Objective To study outcomes of men with mCRPC treated with low-dose AA and/or with prior exposure to KT. Patients and methods Retrospective chart review of all men treated with AA at the Princess Margaret Cancer Centre between November 2009 and March 2013. Outcome measures were prostate-specific antigen response rate (PSA-RR), biochemical progression-free survival (bPFS), treatment duration and overall survival (OS). Associations between AA dose or prior KT and outcomes were assessed using chi-square test for PSA-RR and log-rank test for bPFS, treatment duration and OS. Results In total, 111 men who received AA were evaluable, of which 21 received low-dose AA and 23 received prior KT. There was a non-significant difference in PSA-RR (43% versus 32%, p = 0.37), but no significant differences in median bPFS, median treatment duration and median OS (18.7 versus 16.6 months, p = 0.25) in the full and low-dose cohorts respectively, and for those who received prior KT or not (PSA-RR 48% versus 38%, p = 0.4; median OS 24.2 versus 16.5 months, p = 0.066, respectively). Conclusions Low-dose AA or prior KT treatment were not associated with poorer outcome in men with mCRPC treated with AA. These observations may have implications for drug sequencing and dose in resource-limited settings.
    European Journal of Cancer 09/2014; · 4.82 Impact Factor
  • Journal of Clinical Oncology 08/2014; · 17.88 Impact Factor
  • Ian Tannock, Gregory Pond
    Annals of Oncology 08/2014; · 6.58 Impact Factor
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    ABSTRACT: BACKGROUND Abiraterone acetate (AA), oral CYP17 inhibitor, is an active agent in the treatment of metastatic castrate-resistant prostate cancer (mCRPC).METHODS We (R.L.A and N.A) retrospectively evaluated outcome in 12 men who were re-treated with AA following prior treatment with AA at the Princess Margaret Cancer Centre.RESULTSAll men were heavily pre-treated for mCRPC with a median of four prior lines of therapy, one of which was AA (given either pre- or post-chemotherapy). Eleven out of 12 (92%) men stopped their first treatment course of AA due to progression and one stopped for financial reasons. Seven men had a PSA decrease ≥50% following their first AA treatment, of which three (46%) had a PSA decrease ≥50% to AA re-treatment. The responses to AA re-treatment were generally short-lived with a median biochemical progression-free survival of 2.3 months and median treatment duration of 3.2 months. No PSA responses to AA re-treatment were seen in five men who did not have an initial PSA response to AA.CONCLUSIONS Our data suggest that AA re-challenge may have limited benefit in select men with mCRPC, and warrants further formal research. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 08/2014; · 3.57 Impact Factor
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    ABSTRACT: The neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, has been reported to be a poor prognostic indicator in prostate cancer. Here we explore the use of the NLR to establish a simple prognostic score for men with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel.
    Cancer 07/2014; · 4.90 Impact Factor
  • Breast Cancer Research and Treatment 07/2014; Jul;(2):(146):235-44.. · 4.20 Impact Factor
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    ABSTRACT: Few articles have documented regimens and timing of peri-operative chemotherapy for bladder cancer in routine practice. Here we describe practice patterns in the general population of Ontario, Canada.
    Annals of Oncology 06/2014; · 6.58 Impact Factor
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    ABSTRACT: Clinical data supporting the use of targeted agents for the treatment of metastatic renal cell carcinoma (RCC) are based predominantly on patients with clear cell histology. Little is known about the efficacy of these drugs in non-clear cell variants.
    European Urology 05/2014; · 12.48 Impact Factor
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    ABSTRACT: Background: Inflammation influences cancer development and progression. An elevated platelet/lymphocyte ratio (PLR), a marker of inflammation, has been linked to poor prognosis in several malignancies. Here we quantify the prognostic impact of this biomarker. Methods: A systematic review of databases was conducted to identify publications exploring the association of blood PLR and overall survival (OS) in solid tumors. Data were pooled in a meta-analysis. Pooled HRs for OS by disease group and by PLR cut-off groups were computed and weighted using generic inverse-variance and random-effect modeling. Results: Twenty studies comprising 12,754 patients were assessed. Cut-offs for PLR defining risk groups ranged from 150 to 300 and were dichotomous (12 studies, [group 1]) or split into 3 groups (<150/150-300/>300, 8 studies, [group 2]). Higher PLR was associated with significantly worse OS in group 1 (HR=1.87; 95%CI: 1.49-2.34, P<0.001) and with a non-significant association in group 2 (HR per higher category=1.21, 95%CI: 0.97-1.50; P=0.10). The size of effect of PLR on OS was greater for metastatic disease (HR[group 1]=2.0, 95%CI: 1.6-2.7; HR[group 2]=1.6, 95%CI: 1.1-2.4) than for early stage disease (HR[group 1]=1.5, 95%CI: 1.0-2.2; HR[group 2]=1.0, 95%CI: 0.8-1.3). A significant association was observed for colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma in group 1 and for colorectal cancers in group 2. Conclusion: A high PLR is associated with worse OS in various solid tumors. Further research of its regulation and relevance in daily practice is warranted. Impact: PLR is a readily available and inexpensive biomarker with independent prognostic value in solid tumors.
    Cancer Epidemiology Biomarkers & Prevention 05/2014; · 4.56 Impact Factor
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    Ian F Tannock
    European Urology 04/2014; 65(4):846-7. · 10.48 Impact Factor
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    ABSTRACT: BACKGROUND Practice guidelines recommend neoadjuvant chemotherapy (NACT) for bladder cancer. However, the evidence in support of adjuvant chemotherapy (ACT) is less robust. Here we describe whether the evidence of efficacy for NACT/ACT was sufficient to change clinical practice and whether the efficacy demonstrated in clinical trials was translated into effectiveness in the general population.METHODS Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with bladder cancer treated with cystectomy in Ontario 1994-2008. Utilization of NACT/ACT was compared across 1994-1998, 1999-2003, and 2004-2008. Logistic regression was used to analyze factors associated with NACT/ACT. Cox model and propensity score analyses were used to explore the association between ACT and survival.RESULTSTwo thousand forty-four patients underwent cystectomy for muscle-invasive bladder cancer (MIBC). Use of NACT remained stable (mean, 4%), whereas utilization of ACT increased over time (16%, 18%, 22%; P = .001). Advanced stage (T3/T4; OR, 1.83; 95% CI, 1.38-2.46) and node-positive disease (OR, 8.10; 95% CI, 6.20-10.7) were associated with greater utilization of ACT. Five-year overall survival (OS) and cancer-specific survival (CSS) for all patients was 29% (95% CI, 28%-31%) and 33% (95% CI, 31%-35%), respectively. Utilization of ACT was associated with improved OS (HR, 0.71; 95% CI, 0.62-0.81) and CSS (HR, 0.73; 95% CI, 0.64-0.84). Results were consistent in propensity score analyses.CONCLUSIONSNACT remains substantially underutilized in routine clinical practice. Our results suggest that perioperative chemotherapy is associated with a substantial survival benefit in the general population. Patients who are planning to undergo cystectomy for bladder cancer should be reviewed by a multidisciplinary team. Cancer 2013. © 2013 American Cancer Society.
    Cancer 04/2014; · 5.20 Impact Factor
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    ABSTRACT: Studies assessing cognitive functioning in women treated for breast cancer have used primarily standardized neuropsychological tests and examined accuracy and/or reaction time as outcome measures: they have been inconsistent in identifying the cognitive domains affected and the severity of deficits. In other contexts of neural development and disorders, measures of Intra-individual variability (IIV) have proven useful in identifying subtleties in performance deficits that are not captured by measures of central tendency. This article presents proof of concept that assessing IIV may also increase understanding of the cognitive effects of cancer treatment. We analyzed mean accuracy and reaction time, as well as IIV from 65 women with breast cancer and 28 age and education matched controls who performed the Conner's Continuous Performance Test, a "Go-NoGo" task. Although there were no significant differences between groups using measures of central tendency, there was a group × inter-stimulus interval (ISI) interaction for IIV Dispersion (p < .001). Patient Dispersion was more variable at shorter ISI than controls and less variable at long ISI, suggesting greater sensitivity to presentation speed. Interpretation of IIV differences requires further investigation. Our results suggest that future studies would benefit from designs that allow analysis of IIV measures in studies assessing cognition in cancer survivors. (JINS, 2014, 20, 1-11).
    Journal of the International Neuropsychological Society 03/2014; · 2.70 Impact Factor

Publication Stats

14k Citations
3,016.84 Total Impact Points


  • 2012–2014
    • University Health Network
      • Department of Medical Oncology
      Toronto, Ontario, Canada
  • 2010–2014
    • Hospital Universitario de Albacete
      Albacete, Castille-La Mancha, Spain
    • Baylor College of Medicine
      Houston, Texas, United States
  • 1984–2014
    • University of Toronto
      • • Department of Medical Biophysics
      • • Department of Medicine
      • • Department of Radiation Oncology
      Toronto, Ontario, Canada
  • 1983–2014
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2013
    • CancerCare Manitoba
      Winnipeg, Manitoba, Canada
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
    • University of Cambridge
      • Institute of Cancer Research UK, Cambridge Institute
      Cambridge, England, United Kingdom
    • National Cancer Institute (USA)
      Maryland, United States
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2008–2013
    • Queen's University
      • Division of Cancer Care and Epidemiology
      Kingston, Ontario, Canada
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom
    • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2011–2012
    • Institute of Oncology Ljubljana
      Lubliano, Ljubljana, Slovenia
    • Weill Cornell Medical College
      • Division of Hospital Medicine
      New York City, New York, United States
    • Autonomous University of Nuevo León
      San Nicolás de los Garza, Nuevo León, Mexico
  • 2007
    • Duke University Medical Center
      • Duke Comprehensive Cancer Center
      Durham, NC, United States
    • Centre François Baclesse
      Caen, Lower Normandy, France
  • 2006
    • Trent University
      • Department of Psychology
      Peterborough, Ontario, Canada
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 2003
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
    • Dana-Farber Cancer Institute
      • Center for Outcomes and Policy Research
      Boston, MA, United States
  • 1988–1998
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada