Ian F Tannock

University Health Network, Toronto, Ontario, Canada

Are you Ian F Tannock?

Claim your profile

Publications (315)2871 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Journal of the National Cancer Institute. 12/2014; 106(12).
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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 : official journal of the American Society of Clinical Oncology. 09/2014;
  • [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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; · 7.38 Impact Factor
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2014;
  • Ian Tannock, Gregory Pond
    Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 08/2014;
  • [Show abstract] [Hide abstract]
    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; · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 5.20 Impact Factor
  • Breast Cancer Research and Treatment 07/2014; Jul;(2):(146):235-44.. · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    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 : official journal of the European Society for Medical Oncology / ESMO. 06/2014;
  • [Show abstract] [Hide abstract]
    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;
  • [Show abstract] [Hide abstract]
    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 &amp Prevention 05/2014; · 4.56 Impact Factor
  • Source
    Ian F Tannock
    European Urology 04/2014; 65(4):846-7. · 10.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with advanced cancer have reduced quality of life, which tends to worsen towards the end of life. We assessed the effect of early palliative care in patients with advanced cancer on several aspects of quality of life. The study took place at the Princess Margaret Cancer Centre (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. 24 medical oncology clinics were cluster randomised (in a 1:1 ratio, using a computer-generated sequence, stratified by clinic size and tumour site [four lung, eight gastrointestinal, four genitourinary, six breast, two gynaecological]), to consultation and follow-up (at least monthly) by a palliative care team or to standard cancer care. Complete masking of interventions was not possible; however, patients provided written informed consent to participate in their own study group, without being informed of the existence of another group. Eligible patients had advanced cancer, European Cooperative Oncology Group performance status of 0-2, and a clinical prognosis of 6-24 months. Quality of life (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being [FACIT-Sp] scale and Quality of Life at the End of Life [QUAL-E] scale), symptom severity (Edmonton Symptom Assessment System [ESAS]), satisfaction with care (FAMCARE-P16), and problems with medical interactions (Cancer Rehabilitation Evaluation System Medical Interaction Subscale [CARES-MIS]) were measured at baseline and monthly for 4 months. The primary outcome was change score for FACIT-Sp at 3 months. Secondary endpoints included change score for FACIT-Sp at 4 months and change scores for other scales at 3 and 4 months. This trial is registered with ClinicalTrials.gov, number NCT01248624. 461 patients completed baseline measures (228 intervention, 233 control); 393 completed at least one follow-up assessment. At 3-months, there was a non-significant difference in change score for FACIT-Sp between intervention and control groups (3·56 points [95% CI -0·27 to 7·40], p=0·07), a significant difference in QUAL-E (2·25 [0·01 to 4·49], p=0·05) and FAMCARE-P16 (3·79 [1·74 to 5·85], p=0·0003), and no difference in ESAS (-1·70 [-5·26 to 1·87], p=0·33) or CARES-MIS (-0·66 [-2·25 to 0·94], p=0·40). At 4 months, there were significant differences in change scores for all outcomes except CARES-MIS. All differences favoured the intervention group. Although the difference in quality of life was non-significant at the primary endpoint, this trial shows promising findings that support early palliative care for patients with advanced cancer. Canadian Cancer Society, Ontario Ministry of Health and Long Term Care.
    The Lancet 02/2014; · 39.21 Impact Factor
  • Source
    C M Booth, I F Tannock
    British Journal of Cancer 02/2014; 110(3):551-5. · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abiraterone acetate (abiraterone) prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study's objective was to retrospectively identify factors associated with prostate-specific antigen (PSA) response to abiraterone and validate them in an independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR), thought to be an indirect manifestation of tumor-promoting inflammation, may be associated with response to abiraterone. All patients receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March 2013 were reviewed. The primary end point was confirmed PSA response defined as PSA decline ≥50% below baseline maintained for ≥3 weeks. Potential factors associated with PSA response were analyzed using univariate and multivariable analyses to generate a score, which was then evaluated in an independent cohort from Royal Marsden (RM) NHS foundation. A confirmed PSA response was observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%-50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate dehydrogenase, an NLR ≤ 5 and restricted metastatic spread to either bone or lymph nodes were each associated with PSA response. In multivariable analysis, only low NLR and restricted metastatic spread remained statistically significant. A score derived as the sum of these two categorical variables was associated with response to abiraterone (P = 0.007). Logistic regression analysis on an independent validation cohort of 245 patients verified that this score was associated with response to abiraterone (P = 0.003). It was also associated with OS in an exploratory analysis. A composite score of baseline NLR and extent of metastatic spread is associated with PSA response to abiraterone and OS. Our data may help understand the role of systemic inflammation in mCRPC and warrant further research.
    Annals of Oncology 01/2014; · 7.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Prostate cancer is a disease of older men. Weekly docetaxel (DPq1w) is often favored over the standard three-weekly regimen (DPq3w) due to concerns about safety and tolerability in this population. Materials and Methods Two subgroup analyses of TAX 327 were conducted. Among patients receiving DPq3w, tolerability and efficacy were compared between three age groups: < 65, 65–74 and ≥ 75 years. For men ≥ 75 years, these outcomes were compared between DPq3w, DPq1w, and mitoxantrone (MP) arms. Tolerability outcomes included dose delivery, grade 3/4 adverse events and quality of life. Efficacy outcomes included overall survival and tumor response. Results Of 1006 men with metastatic castrate-resistant prostate cancer (mCRPC) in the trial, 335 received DPq3w. Among these, 20% were age ≥ 75 years. For DPq3w, there were non-significant associations of worse tolerability and efficacy with advancing age. Twenty-eight percent of men age ≥ 75 years had an objective pain response, compared to 38% and 34% of patients 65–74 and < 65 years, respectively. There were no significant differences in prostate-specific antigen (PSA) response (43–48%, p = 0.74) or measurable tumor response (7–17%, p = 0.30) according to age. Among men ≥ 75 years, DPq3w resulted in more dose reductions than DPq1w (22% versus 8%, p = 0.007), but tolerability was otherwise comparable. Both were associated with more favorable efficacy than mitoxantrone. Conclusions Tolerability and efficacy of DPq3w appear less favorable with advancing age. Compared to DPq1w, DPq3w is associated with better survival outcomes, but similar tolerability, and remains the standard first-line chemotherapy option in mCRPC. Toxicity is substantial, therefore careful patient selection, close monitoring and early management of toxicities is advised.
    Journal of Geriatric Oncology 01/2014; · 1.12 Impact Factor

Publication Stats

13k Citations
2,871.00 Total Impact Points

Institutions

  • 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