Ian F Tannock

University of Toronto, Toronto, Ontario, Canada

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Publications (370)3684.31 Total impact

  • Source
    Andrea S Fung · Carol Lee · Man Yu · Ian F Tannock
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    ABSTRACT: The growth of solid tumors and their regrowth after treatment is dependent upon functional tumor vasculature. Some chemotherapeutic agents have shown anti-angiogenic properties but there are limited studies of the effect of chemotherapy on tumor vasculature. Here we investigate the effect of paclitaxel, 5-fluorouracil (5-FU) and doxorubicin on tumor vasculature in subcutaneous and orthotopic xenografts in mice The vascular density and percentage of functional blood vessels were evaluated in subcutaneous A431 human vulvar cancer xenografts, and in subcutaneous and orthotopic MCF-7 human breast cancer xenografts, following single doses of paclitaxel, 5-FU or doxorubicin There was no significant difference in total (CD31+) blood vessels between untreated ectopic and orthotopic MCF-7 tumors, but there was a significantly lower proportion of functional blood vessels in orthotopic tumors. After paclitaxel treatment, there was a decrease in functional tumor vasculature in A431 subcutaneous xenografts, followed by a subsequent rebound. There was a significant decrease in total vascular density on day 12 in A431 tumors following 5-FU or doxorubicin treatment, but no change in the percentage of functional vessels. An increase in functional blood vessels or percentage of functional vasculature was noted in MCF-7 subcutaneous and orthotopic xenografts following chemotherapy treatment There are differences in the vasculature and microenvironment of ectopic and orthotopic xenografts in mice. Anti-tumor effects of chemotherapy may be due, in part, to effects on tumor vasculature and may vary in different tumor models.
    BMC Cancer 12/2015; 15(1):1091. DOI:10.1186/s12885-015-1091-6 · 3.36 Impact Factor
  • Man Yu · Carol Lee · Marina Wang · Ian F Tannock
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    ABSTRACT: Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined effects of the PPI, lansoprazole, to modify the activity of doxorubicin. To gain insight into mechanisms, we studied effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole displayed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Cancer Science 07/2015; DOI:10.1111/cas.12756 · 3.52 Impact Factor
  • Qian Tan · Jasdeep K Saggar · Man Yu · Marina Wang · Ian F Tannock
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    ABSTRACT: Drug resistance can occur at the individual cellular level or as a result of properties of the tumor microenvironment. The convoluted vasculature within tumors results in robustly proliferating well-nourished cells located proximal to functional blood vessels and regions of slowly proliferating (often hypoxic) cells located distal to functional blood vessels. Irregular blood flow and large distances between functional blood vessels in solid tumors lead to poor drug distribution within them such that cells distal from functional blood vessels are exposed to ineffective concentrations of drug, resulting in therapeutic resistance. Strategies to improve or complement the distribution of anticancer drugs within tumors hold promise for increasing antitumor effects without corresponding increases in normal tissue toxicity. In particular, use of hypoxia-targeted agents and modulation of autophagy have shown promising results in enhancing the distribution of drug activity within solid tumors and hence antitumor efficacy. In this review, we describe causes of resistance to chemotherapy that relate to the microenvironment of solid tumors and the potential to improve antitumor effects by countering such mechanisms of resistance.
    The Cancer Journal 07/2015; 21(4):254-62. DOI:10.1097/PPO.0000000000000131 · 4.24 Impact Factor
  • Multinational Association for the Supportive Care in Cancer Annual Meeting, Copenhagen, Denmark; 06/2015
  • Christopher M Booth · Ian F Tannock
    06/2015; 1(6). DOI:10.1001/jamaoncol.2015.1210
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    ABSTRACT: The mechanisms underlying the favourable prognosis of androgen receptor (AR) expression in breast cancer are unknown. The associations between the 21-gene recurrence score (RS), AR, grade, mitotic score, Ki-67 and estrogen receptor (ER) and progesterone receptor (PgR) expression were explored in sequential women with lymph node-negative, ER-positive and HER2-negative breast cancer. Statistical significance of this exploratory study was defined as p<0.10. Analysis comprised 70 women. Most tumours had high AR expression (97% had scores >3). Median RS was 15 (range 1-53). AR expression showed a minimally significant positive correlation with ER (R=0.37), but no correlation with Ki-67 (R=-0.18). In univariable analysis, AR (p=0.01), ER (p<0.001) and PgR (p<0.001) had significant negative associations with RS. Ki-67 (p=0.16), grade (p=0.40) and mitotic score (p=0.23) showed no association with RS. Multivariable analysis showed similar associations. AR is associated with lower RS, but not with Ki-67. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of clinical pathology 06/2015; 68(10). DOI:10.1136/jclinpath-2015-203012 · 2.92 Impact Factor
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    ABSTRACT: Much progress has been made in research for prostate cancer in the past decade. There is now greater understanding for the genetic basis of familial prostate cancer with identification of rare but high-risk mutations (eg, BRCA2, HOXB13) and low-risk but common alleles (77 identified so far by genome-wide association studies) that could lead to targeted screening of patients at risk. This is especially important because screening for prostate cancer based on prostate-specific antigen remains controversial due to the high rate of overdiagnosis and unnecessary prostate biopsies, despite evidence that it reduces mortality. Classification of prostate cancer into distinct molecular subtypes, including mutually exclusive ETS-gene-fusion-positive and SPINK1-overexpressing, CHD1-loss cancers, could allow stratification of patients for different management strategies. Presently, men with localised disease can have very different prognoses and treatment options, ranging from observation alone through to radical surgery, with few good-quality randomised trials to inform on the best approach for an individual patient. The survival of patients with metastatic prostate cancer progressing on androgen-deprivation therapy (castration-resistant prostate cancer) has improved substantially. In addition to docetaxel, which has been used for more than a decade, in the past 4 years five new drugs have shown efficacy with improvements in overall survival leading to licensing for the treatment of metastatic castration-resistant prostate cancer. Because of this rapid change in the therapeutic landscape, no robust data exist to inform on the selection of patients for a specific treatment for castration-resistant prostate cancer or the best sequence of administration. Moreover, the high cost of the newer drugs limits their widespread use in several countries. Data from continuing clinical and translational research are urgently needed to improve, and, crucially, to personalise management.
    The Lancet 06/2015; DOI:10.1016/S0140-6736(14)61947-4 · 45.22 Impact Factor
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    ABSTRACT: Full Text Avail for Limited Time: http://authors.elsevier.com/a/1RCcR_3r0J3Zr7 The heterogeneous intra-tumoral accumulation of liposomes has been linked to both the chaotic tumor microcirculation and to elevated interstitial fluid pressure (IFP). Here, we explored the relationship between tumor microcirculation, IFP, and the intra-tumoral accumulation of liposomes. Measurements of the tumor microcirculation using perfusion imaging, IFP using a novel image-guided robotic needle positioning system, and the intra-tumoral distribution of liposomes using volumetric micro-CT imaging were performed in mice bearing subcutaneous and orthotopic MDA-MB-231 tumors. Intra-tumoral perfusion and IFP were substantially different between the two tumor implantation sites. Tumor perfusion and not vascular permeability was found to be the primary mediator of the intra-tumoral accumulation of CT-liposomes. A strong relationship was observed between the radial distribution of IFP, metrics of tumor perfusion, and the intra-tumoral accumulation of liposomes. Tumors with elevated central IFP that decreased at the periphery had low perfusion and low levels of CT-liposome accumulation that increased towards the periphery. Conversely, tumors with low and radially uniform IFP exhibited higher levels of tumor perfusion and CT-liposome accumulation. Both tumor perfusion and elevated IFP exhibit substantial intra-tumoral heterogeneity and both play an integral role in mediating the intra-tumoral accumulation of liposomes through a complex interactive effect. Measuring IFP in the clinical setting remains challenging and these results demonstrate that tumor perfusion imaging alone provides a robust non-invasive method to identify factors that contribute to poor liposome accumulation and may allow for pre-selection of patients that are more likely to respond to nanoparticle therapy. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 06/2015; 211. DOI:10.1016/j.jconrel.2015.06.008 · 7.71 Impact Factor
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    ABSTRACT: The first St.Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection.Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with advanced prostate cancer in clinical trials should be encouraged. © The Author 2015. 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 06/2015; 26(8). DOI:10.1093/annonc/mdv257 · 7.04 Impact Factor
  • American society of clinical oncology annual conference, Chicago, Illinois, USA; 05/2015
  • Source
    K Fizazi · C Jenkins · I F Tannock
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    ABSTRACT: Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to men with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of patient survival. The GETUG-AFU-15 and CHAARTED studies both assessed the efficacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in men with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (∼75%) and patients who developed metastases following treatment for localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUG-AFU-15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to 9 cycles; CHAARTED 6 cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT vs ADT alone. The GETUG-AFU-15 did not find a significant difference in the primary endpoint of overall survival (hazard ratio [HR] 0.9 [95% Confidence Interval [CI] 0.7, 1.2; P=0.44) for ADT plus docetaxel vs ADT alone. The CHAARTED study met the primary endpoint of overall survival (HR 0.61 [95% CI 0.47, 0.80]; P=0.0003), and in a subset analysis reported the greatest improvement in overall survival for patients with high-volume disease (HR 0.60 [95% CI 0.45, 0.81] P=0.0006). The following article debates the results from the GETUG-AFU-15 and CHAARTED studies and asks whether medical practice should be changed for patients with metastatic hormone-naive prostate cancer based on the results of one positive study. © The Author 2015. 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 05/2015; 26(8). DOI:10.1093/annonc/mdv245 · 7.04 Impact Factor
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    ABSTRACT: This study examined the impact of androgen-deprivation therapy (ADT) on physical function and quality of life (QOL) over 36 months. Eighty-seven men with nonmetastatic prostate cancer (PC) who were starting continuous ADT and 2 control groups (86 PC controls without ADT and 86 healthy controls), matched by age and education, were enrolled. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and Timed Up and Go (TUG) test. QOL was measured with the 36-Item Short Form Health Survey of the Medical Outcomes Study. Subjects were assessed at the baseline and at 3, 6, 12, 18, 24, 30, and 36 months. Mixed effects regression models were fitted with adjustments for baseline covariates. The 6MWT distance improved initially and then stabilized in both control groups but remained unchanged for ADT users (P = .0030). Grip strength remained stable in control groups but declined sharply in the ADT group by 3 months and then remained stable to 36 months (P = .0041). TUG scores declined gradually in the ADT group over 36 months but were unchanged in control groups (P = .0008). Aggregate physical QOL declined in ADT users over time but remained stable in control groups (P = .0001). Aggregate mental QOL was stable in all groups. Declines seen in the first year of ADT use generally persisted over 36 months and were independent of age. Previously noted physical side effects over the first 12 months of ADT persisted or continued to worsen over an additional 2 years with no evidence of recovery. Exercise interventions to counteract these declines may be warranted. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    Cancer 03/2015; 121(14). DOI:10.1002/cncr.29355 · 4.89 Impact Factor
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    ABSTRACT: Progression-free survival and time-to-progression (PFS/TTP) are used commonly as primary end-points in trials evaluating treatments for metastatic breast cancer (MBC). We reviewed the impact of censoring on interpretation of these end-points. A systematic review identified phase 3 trials in MBC published between 2001 and 2012 that reported hazard ratios (HRs) for PFS/TTP and Kaplan-Meier curves indicating numbers at risk. We calculated HRs for time-to-treatment-failure (TTF) where discontinuation of treatment for any reason is considered an event. Mean HRs for PFS/TTP, TTF, and overall survival (OS) were 0.79, 0.89 and 0.91, respectively. Unbalanced censoring of patients prior to progression was prevalent, usually with more patients censored in the experimental arms. There was moderate-to-poor correlation of HRs of PFS/TTP and TTF with HRs for OS. We suggest that TTF should be reported as supportive analysis in registration trials and extent of missing data due to censoring be considered in decisions made by regulatory agencies. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 02/2015; 51(6). DOI:10.1016/j.ejca.2014.12.016 · 5.42 Impact Factor
  • Jasdeep K Saggar · Ian F Tannock
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    ABSTRACT: Purpose: Chemotherapy targets rapidly-proliferating tumor cells, but spares slowly-proliferating hypoxic cells. We hypothesized that nutrition of hypoxic cells would improve in intervals between chemotherapy, and that hypoxic cells destined to die without treatment would survive and proliferate. Experimental Design: We therefore evaluated repopulation and reoxygenation following chemotherapy, and the effects of the hypoxia-activated pro-drug TH-302 on these processes. Tumor-bearing mice were treated with doxorubicin or docetaxel +/- TH-302. Pimonidazole (given concurrent with chemotherapy) and EF5 (given 24-120 hours later) identified hypoxic cells. Proliferation (Ki67) and oxygen status (EF5 uptake) of formerly hypoxic (pimo+ve) cells were quantified by immunohistochemistry. Results: Chronically hypoxic cells had limited proliferation in control tumors. After chemotherapy, we observed reoxygenation and increased proliferation of previously hypoxic cells; these processes were inhibited by TH-302. Conclusions: Chemotherapy leads to paradoxical sparing of hypoxic cells destined to die in solid tumors in absence of treatment, and their reoxygenation and proliferation: TH-302 inhibits these processes. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 02/2015; 75(1 Supplement). DOI:10.1158/1078-0432.CCR-14-2298 · 8.72 Impact Factor
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    ABSTRACT: To assess radical cystectomy (RC) outcomes and adjuvant chemotherapy (ACT) use in the elderly in routine practice. Bladder cancer occurs most commonly in the elderly. RC, standard treatment for muscle-invasive bladder cancer, presents challenges in older patients. Suboptimal evidence guides ACT use. All patients undergoing RC for urothelial cancer in Ontario from 1994 to 2008 were identified using the Ontario Cancer Registry. Pathology reports and treatment records were linked to the database. Patients were age stratified as <70, 70-74, 75-79 and ≥80 years. Logistic regression and Cox proportional hazards identified associations with and effectiveness of ACT use. We identified 3320 patients: 1362 (41%) aged <70 years; 674 (20%) aged 70-74 years; 674 (19%) aged 75-79 years, and 657 (20%) aged ≥80 years. Thirty-day (1%, 2%, 2%, 6%; P <.0001) and 90-day (5%, 8%, 9%, 15%; P <.0001) mortality increased with age. Age-stratified 5-year cancer-specific survival was 42%, 37%, 34%, and 32%, respectively (P <.001); 5-year overall survival was 40%, 34%, 28%, and 23%, respectively (P <.001). ACT decreased with age (27%, 16%, 12%, 5%; P <.0001). Among ACT patients, 87% aged <70 years received cisplatin vs 73% aged ≥70 years (P = .003). ACT was associated with improved cancer-specific survival (hazard ratio [HR] = 0.73 and 95% confidence interval [CI] = 0.59-0.89 for age <70 years and HR = 0.73 [95% CI = 0.59-0.89] for ≥70 years) and overall survival (HR = 0.70 [95% CI = 0.58-0.85] for age <70 years and HR = 0.70 [95% CI = 0.59-0.84] for ≥70 years) across all age groups. Cystectomy carries a higher risk of postoperative mortality in elderly patients in routine clinical practice. ACT is used infrequently in older patients despite a substantial survival benefit observed across all age groups. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urology 02/2015; 85(4). DOI:10.1016/j.urology.2014.12.027 · 2.19 Impact Factor
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    ABSTRACT: Background: Autophagy allows recycling of cellular components and may facilitate cell survival after chemotherapy. Pantoprazole inhibits proton pumps and is reported to inhibit autophagy. Here we evaluate the effects of pantoprazole to modify cytotoxicity of the anticancer drug docetaxel, and underlying mechanisms. Methods: Effects of docetaxel±pantoprazole were studied against wild-type and autophagy-deficient PC3 cells and against four human xenografts. Effects of pantoprazole on autophagy were evaluated by quantifying LC3-I, LC3-II and p62 proteins in western blots, and by fluorescent microscopy of cells transfected with RFP-GFP-LC3. The distribution of drug effects and of autophagy was quantified in tumour sections in relation to blood vessels and hypoxia by immunohistochemistry using γH2AX, cleaved caspase-3, Ki67 and LC3/ p62. Results: Pantoprazole increased the toxicity of docetaxel in vitro, increased docetaxel-induced expression of γH2AX and cleaved caspase-3, and decreased Ki67 in tumour sections. Pantoprazole increased growth delay of four human xenografts of low, moderate and high sensitivity to docetaxel, with minimal increase in toxicity. Docetaxel led to increased autophagy throughout tumour sections. Pantoprazole inhibited autophagy, and effects of pantoprazole were reduced against genetically modified cells with decreased ability to undergo autophagy. Conclusions: Autophagy is a mechanism of resistance to docetaxel chemotherapy that may be modified by pantoprazole to improve therapeutic index.
    British Journal of Cancer 02/2015; 112(5). DOI:10.1038/bjc.2015.17 · 4.84 Impact Factor
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    ABSTRACT: Cancer is not one disease. Outcomes and endpoints in trials should incorporate the therapeutic modality and cancer type because these factors affect clinician and patient expectations. In this Review, we discuss how to: define the importance of endpoints; make endpoints understandable to patients; improve the use of patient-reported outcomes; advance endpoints to parallel changes in trial design and therapeutic interventions; and integrate these improvements into trials and practice. Endpoints need to reflect benefit to patients, and show that changes in tumour size either in absolute terms (response and progression) or relative to control (progression) are clinically relevant. Improvements in trial design should be accompanied by improvements in available endpoints. Stakeholders need to come together to determine the best approach for research that ensures accountability and optimises the use of available resources. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 01/2015; 16(1):e43-e52. DOI:10.1016/S1470-2045(14)70380-8 · 24.69 Impact Factor
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    R Leibowitz-Amit · L Khoja · I F Tannock · A M Joshua
    Annals of Oncology 01/2015; 26(5). DOI:10.1093/annonc/mdv039 · 7.04 Impact Factor
  • Gordon Winocur · J Martin Wojtowicz · Ian F Tannock
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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; 281. DOI:10.1016/j.bbr.2014.12.028 · 3.03 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; 26(4). DOI:10.1093/annonc/mdu569 · 7.04 Impact Factor

Publication Stats

19k Citations
3,684.31 Total Impact Points


  • 1984–2015
    • University of Toronto
      • • Department of Medicine
      • • Department of Medical Biophysics
      Toronto, Ontario, Canada
  • 1981–2015
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2002–2014
    • University Health Network
      • Department of Medical Oncology
      Toronto, Ontario, Canada
  • 2013
    • CancerCare Manitoba
      Winnipeg, Manitoba, Canada
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
    • National Cancer Institute (USA)
      Maryland, United States
  • 2010–2013
    • Hospital Universitario de Albacete
      Albacete, Castille-La Mancha, Spain
  • 2008
    • Queen's University
      Kingston, Ontario, Canada
  • 2005
    • University of California, Irvine
      • Chao Family Comprehensive Cancer Center
      Irvine, CA, United States
  • 2003
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 1981–1998
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
  • 1997
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom