- Email: [email protected]
Cardiotoxicity associated with sunitinib
Correspondence
that Chapman selectively directs at one of the few instances of significant health philanthropy emerging from a developing country. I recommend an alternative, evidence-based, and more constructive approach. Serious research should be undertaken to examine the streams of finance to foundations and other non-profit entities that derive from harmful industries, as well as from corporations that do not apply the highest standards of labour rights, gender equity, and environmental security. Based on collective, expert analysis, guidelines could then be produced to promote transparent and ethical behaviour from all parties, in a way that places the pursuit of health equity as the supreme value. This is not, however, the value that emerges from Chapman’s invective. Cultural stereotyping and biased finger-pointing do not serve to advance the worthy cause of the tobacco control movement. Before building himself up into such a harsh judge of others, Chapman would do well to examine the sources of his own prejudiced view of the world. I declare that I have no conflict of interest.
Julio Frenk [email protected] President, Instituto Carso de la Salud, M. A. de Quevedo 24-A, Mailbox 143, México DF 01050, Mexico 1
2
Alleyne G, Aninat E, de Ferranti D, et al. Instituto Carso de la Salud: a boost for health philanthropy. Lancet 2008; 371: 100–01. Chapman S. International tobacco control should repudiate Jekyll and Hyde health philanthropy. Tob Control 2008; 17: 1.
Cardiotoxicity associated with sunitinib Tammy Chu and colleagues’ Article (Dec 15, p 2011)1 reiterates the importance of monitoring the cardiotoxic effects of agents that target growth factor signalling pathways. The 11% cardiovascular event rate Chu and colleagues found is striking, but the proportion of patients with 1244
documented myocardial necrosis (18% had a cardiac troponin I concentration >0·10 μg/L) might be much more telling and could even be an underrepresentation. Depending on the cutoff used to classify myocardial necrosis (99th centile vs the 10% coefficient of variation concentration2) as well as the troponin I assay used (they are not equivalent3), the prevalence of patients with myocardial necrosis could be further increased. Chu and colleagues did not document which troponin I assay was used, the rationale for the cutoff (ie, 0·10 μg/L), nor the temporal relation and frequency of increased cardiac troponin I concentrations among participants (eg, cardiac troponin was measured weekly and rise and fall patterns are indicative of acute injury2). Despite these omissions, the important observation that at least a fifth of patients had increased cardiac troponin concentrations deserves additional attention. Many reports4,5 have documented that detectable concentrations of cardiac troponin are independent predictors of future long-term cardiovascular events (eg, myocardial infarction, heart failure, death) in healthy populations and in patients with acute coronary syndrome. As drugs evolve from cytotoxic agents to inhibitors of signalling pathways, we must be cognisant of the fact that patients who survive the initial course of treatment without any evident cardiovascular toxic effects might still be at risk, depending on their cardiac troponin concentration. PAK has received speakers’ honoraria and research funding from Beckman Coulter. SH has received honoraria, research funding, and consultancy from Pfizer.
*Peter A Kavsak, Sebastien Hotte [email protected] Departments of Pathology and Molecular Medicine (PAK) and Department of Oncology (SH), McMaster University, Hamilton, Ontario L8N 3Z5, Canada 1
Chu TF, Rupnic MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007; 370: 2011–19.
2
3
4
5
Kavsak PA, MacRae AR, Lustig V, et al. The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction. Am Heart J 2006; 152: 118–25. Venge P, Lagerqvist B, Diderholm E, Lindahl B, Wallentin L. Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy). Am J Cardiol 2002; 89: 1035–41. Zethelius Z, Johnston N, Venge P. Troponin I as a predictor of coronary heart disease and mortality in 70-year old men: a communitybased cohort study. Circulation 2006; 113: 1071–78. Kavsak PA, Newman AM, Lustig V, et al. Longterm health outcomes associated with detectable troponin I concentrations. Clin Chem 2007; 53: 220–27.
Pfizer is committed to making important safety information about sunitinib malate available to physicians and patients. Tammy Chu and colleagues’ retrospective subanalysis of 75 patients from a previously reported phase I/II trial in gastrointestinal stromal tumour (GIST)1 provides valuable information for the management of patients taking sunitinib who have limited treatment options. The findings underscore the importance of a collaborative team of health-care professionals working together. We believe it is important that physicians monitor patients closely for these generally manageable cardiovascular events, especially those with a history of cardiovascular disorders. All patients in this subanalysis had received previous imatinib therapy and 20% had received anthracyclines, both of which can be associated with cardiotoxic effects. Cardiovascular effects with sunitinib were seen with a lower frequency in randomised phase III studies in renal cell carcinoma (RCC)2 and GIST3 and are reported in the approved labelling, along with recommendations for monitoring in patients with cardiac risk factors. Pfizer is committed to patients’ safety and maintains a global safety database, monitoring all sponsored trials and spontaneous reports. Pfizer encourages physicians to continue www.thelancet.com Vol 371 April 12, 2008
that Chapman selectively directs at one of the few instances of significant health philanthropy emerging from a developing country. I recommend an alternative, evidence-based, and more constructive approach. Serious research should be undertaken to examine the streams of finance to foundations and other non-profit entities that derive from harmful industries, as well as from corporations that do not apply the highest standards of labour rights, gender equity, and environmental security. Based on collective, expert analysis, guidelines could then be produced to promote transparent and ethical behaviour from all parties, in a way that places the pursuit of health equity as the supreme value. This is not, however, the value that emerges from Chapman’s invective. Cultural stereotyping and biased finger-pointing do not serve to advance the worthy cause of the tobacco control movement. Before building himself up into such a harsh judge of others, Chapman would do well to examine the sources of his own prejudiced view of the world. I declare that I have no conflict of interest.
Julio Frenk [email protected] President, Instituto Carso de la Salud, M. A. de Quevedo 24-A, Mailbox 143, México DF 01050, Mexico 1
2
Alleyne G, Aninat E, de Ferranti D, et al. Instituto Carso de la Salud: a boost for health philanthropy. Lancet 2008; 371: 100–01. Chapman S. International tobacco control should repudiate Jekyll and Hyde health philanthropy. Tob Control 2008; 17: 1.
Cardiotoxicity associated with sunitinib Tammy Chu and colleagues’ Article (Dec 15, p 2011)1 reiterates the importance of monitoring the cardiotoxic effects of agents that target growth factor signalling pathways. The 11% cardiovascular event rate Chu and colleagues found is striking, but the proportion of patients with 1244
documented myocardial necrosis (18% had a cardiac troponin I concentration >0·10 μg/L) might be much more telling and could even be an underrepresentation. Depending on the cutoff used to classify myocardial necrosis (99th centile vs the 10% coefficient of variation concentration2) as well as the troponin I assay used (they are not equivalent3), the prevalence of patients with myocardial necrosis could be further increased. Chu and colleagues did not document which troponin I assay was used, the rationale for the cutoff (ie, 0·10 μg/L), nor the temporal relation and frequency of increased cardiac troponin I concentrations among participants (eg, cardiac troponin was measured weekly and rise and fall patterns are indicative of acute injury2). Despite these omissions, the important observation that at least a fifth of patients had increased cardiac troponin concentrations deserves additional attention. Many reports4,5 have documented that detectable concentrations of cardiac troponin are independent predictors of future long-term cardiovascular events (eg, myocardial infarction, heart failure, death) in healthy populations and in patients with acute coronary syndrome. As drugs evolve from cytotoxic agents to inhibitors of signalling pathways, we must be cognisant of the fact that patients who survive the initial course of treatment without any evident cardiovascular toxic effects might still be at risk, depending on their cardiac troponin concentration. PAK has received speakers’ honoraria and research funding from Beckman Coulter. SH has received honoraria, research funding, and consultancy from Pfizer.
*Peter A Kavsak, Sebastien Hotte [email protected] Departments of Pathology and Molecular Medicine (PAK) and Department of Oncology (SH), McMaster University, Hamilton, Ontario L8N 3Z5, Canada 1
Chu TF, Rupnic MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007; 370: 2011–19.
2
3
4
5
Kavsak PA, MacRae AR, Lustig V, et al. The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction. Am Heart J 2006; 152: 118–25. Venge P, Lagerqvist B, Diderholm E, Lindahl B, Wallentin L. Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy). Am J Cardiol 2002; 89: 1035–41. Zethelius Z, Johnston N, Venge P. Troponin I as a predictor of coronary heart disease and mortality in 70-year old men: a communitybased cohort study. Circulation 2006; 113: 1071–78. Kavsak PA, Newman AM, Lustig V, et al. Longterm health outcomes associated with detectable troponin I concentrations. Clin Chem 2007; 53: 220–27.
Pfizer is committed to making important safety information about sunitinib malate available to physicians and patients. Tammy Chu and colleagues’ retrospective subanalysis of 75 patients from a previously reported phase I/II trial in gastrointestinal stromal tumour (GIST)1 provides valuable information for the management of patients taking sunitinib who have limited treatment options. The findings underscore the importance of a collaborative team of health-care professionals working together. We believe it is important that physicians monitor patients closely for these generally manageable cardiovascular events, especially those with a history of cardiovascular disorders. All patients in this subanalysis had received previous imatinib therapy and 20% had received anthracyclines, both of which can be associated with cardiotoxic effects. Cardiovascular effects with sunitinib were seen with a lower frequency in randomised phase III studies in renal cell carcinoma (RCC)2 and GIST3 and are reported in the approved labelling, along with recommendations for monitoring in patients with cardiac risk factors. Pfizer is committed to patients’ safety and maintains a global safety database, monitoring all sponsored trials and spontaneous reports. Pfizer encourages physicians to continue www.thelancet.com Vol 371 April 12, 2008