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PO-61 Cancer and symptomatic venous thromboembolism rates: VERITY Registry findings
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4th Int. Conf. on Thrombosis and Hemostasis Issues in Cancer / Thrombosis Research 120 Suppl. 2 (2007) S145–S178
88% inhibition at 100 mg/mL. Migration was then visualized in a microfluidic system. When B-CLL cells were introduced in the device and CXCL12 was distributed uniformly throughout the chamber, cells migrated toward the higher concentration of CXCL12. On the contrary, when CXCL12 was preincubated with heparin before loading in the device, cells underwent chemokinesis or unbiased motion. Conclusions: Clinically relevant concentrations of nadroparin inhibit the CXCL12-driven chemotaxis of B-CLL cells. By sequestering CXCL12, nadroparin may affect interactions of leukemia cells with protective microenvironments. PO-59 Low molecular weight heparin (LMWH) versus best supportive care in cancer patients. A meta-analysis of randomized clinical trials S. Laporte1 *, G. Meyer2 , H.R. B¨ uller3 , H. Decousus1,4 , N. Moulin5 , M. Cucherat6 , P. Mismetti1,5 . 1 Dept of clinical pharmacology, EA3065, University Hospital of Saint-Etienne, France, 2 Dept of pulmonology, European Hospital Georges Pompidou, Paris, France, 3 Dept of vascular medicine, Academic Medical Center, Amsterdam, The Netherlands, 4 INSERM CIE3, EA3065, University Hospital of Saint-Etienne, France, 5 Dept. of internal medicine, EA3065, University Hospital of Saint-Etienne, France, 6 Dept of clinical pharmacology, University Hospital of Lyon, France Introduction: Several studies have suggested a possible antitumor effect of LMWH. Meta-analyses have been done but focusing either on VTE patients or on cancer patients free of VTE. In addition, results summarized death rates at a given time rather than survival data, involving a lost of information. Aim: We performed a meta-analysis of randomized clinical trials (RCTs) in cancer patients with or without VTE to assess the potential survival benefit of LMWH compared to best supportive care. Patients and Methods: Medline, Cancerlit, Embase, Google Scholar and Cochrane Library searches were supplemented by abstract of meetings (ASCO, ECCO, ISTH, ASH). We included all RCTs comparing LMWH to best supportive care, i.e. placebo or no treatment in cancer patients free of VTE and VKA in cancer patients with VTE. Hazard ratio (HR) and 95% CI of overall survival was computed with individual patient data when available, directly extracted from publication, or derived from the number of deaths, log-rank p-value or survival curve [Parmar M et al. Stat Med 1998]. Results: A total of 10 RCTs comparing LMWH to best supportive care were found, 6 versus placebo/no treatment in cancer patients free of VTE (912 patients; 2 trials pending), and 4 versus VKA in VTE patients (1120 patients). A significant 13% improvement of overall survival was found with LMWH (HR = 0.87 [0.78; 0.97], P = 0.02), without heterogeneity between trials in patients with or without VTE (P = 0.42). Conclusion: Compared to best supportive care, LMWH seem to increase overall survival in cancer patients. Meta-analysis on individual patient data could improve information regarding the type of cancer and presence of metastases. PO-60 Meta-analysis of randomised comparisons between the effects of warfarin and low molecular weight heparin in thromboprophylaxis and mortality in cancer patients A.M. Young *, L. Gross, R. Hills, K. Wheatley. University of Birmingham Clinical Trials Unit, Birmingham, England Introduction: The role of the low molecular weight heparins and warfarin in the prophylaxis of venous thromboembolism (VTE) in cancer patients remains uncertain. A meta-analysis was performed to determine the effects of warfarin and LMWH on primary and secondary VTE rates and mortality. Methods: Computerised searches in MedLine, NCI Trials Register, ISTH, ASCO and ASH proceedings and reference checks were carried out for papers from 1984 onwards, to Oct 2006. The inclusion criteria
set were: RCTs; medical cancer patients; thromboprophylaxis; warfarin or heparin vs no treatment or placebo or warfarin vs heparin. Standard meta-analysis methods were utilised and results were presented as ORs and CIs with tests for interaction used to determine heterogeneity of treatment effect. Results: 27 trials with 6,320 patients were found to match the criteria; this included thromboprophylaxis in patients with central venous catheters (CVCs); some cancer data were extracted for patients from all disease trials if possible. In 6 trials (n = 1,667) of warfarin vs not, there was no clear evidence of a decrease in VTEs (OR = 0.72, CI = 0.49 1.06, p = 0.09) A total of 9 trials (n = 2,621) had survival data: there was no clear benefit of a decrease in mortality with warfarin (OR = 0.92, CI = 0.82 1.02, p = 0.1). In 7 trials (n = 2,441) of LMWH vs not, VTE was reduced (OR = 0.62, CI = 0.44 0.89, p = 0.009). 5 trials (n = 1,211) contained survival data and mortality was reduced with LMWH (OR = 0.78, CI = 0.67 0.91 p = 0.002). In 8 trials of LMWH vs oral anticoagulation (mainly warfarin), (n = 1,179), VTE rates were less with LMWH (OR = 0.49 CI = 0.35 0.69, p 0.001). No mortality benefit was observed in 10 trials (n = 1,100) (OR = 0.95, CI = 0.80 1.14, p = 0.6). Conclusions: The results of these meta-analyses suggest that LMWH is the preferred form of prophylaxis for VTE in cancer patients and that overall, there may be an anti-tumour effect, leading to a survival benefit.
PO-61 Cancer and symptomatic venous thromboembolism rates: VERITY Registry findings P. Rose1 *, P. Shankara2 , A. McManus3 , Z. Lester4 , T. Nokes4 , T. Farren5 , N. Scriven6 , R. Arya7 , D. O’Shaughnessy8 , for the VERITY Investigators. 1 Warwick Hospital, Warwick; 2 Heart of England NHS Foundation Trust, Birmingham; 3 MMRx Research, London; 4 Derriford Hospital, Plymouth Hospitals NHS Trust; 5 Barts and the London Hospitals, London; 6 The Calderdale Royal Hospital, Halifax; 7 King’s College Hospital, London; 8 Department of Health, London, UK Introduction: VTE rates in specific cancers and its impact on mortality are poorly characterized. VERITY, an ongoing UK prospective VTE treatment registry, has enrolled ~70,000 patients with suspected or confirmed VTE, including >4,000 cancer patients. Aim: We compared VTE rates in cancer and non-cancer patients and the prevalence of different cancer types in VTE-positive and VTEnegative cases. Patients and methods: By July 2007, 69,661 patients had been enrolled. VTE diagnosis was known in 58,810 patients; 26.7% (n = 15,682) had confirmed VTE, 73.3% (n = 43,128) had a diagnosis of VTE excluded and 6.5% (n = 3,832) had cancer. Results: Cancer was >3 times more prevalent in the VTE population than the non-VTE patients 13.5% (2,116/15,682) vs. 4% (1716/43128), respectively. Comparing cancer to noncancer patients, VTE was 2-fold higher in cancer patients (55.2% [2,116/3,832] vs. 24.9% [13,566/54,474], respectively). The most common forms of cancer (breast, prostate, colorectal and lung) matched the cancers most commonly diagnosed with VTE (1,064 cases, or 50.3% of all cancer cases with VTE). However, calculating the ratio of the incidence of each cancer type in the VTE patients to the non-VTE patients offers a different insight into which cancers are particularly apparent in the VTE population. The ratio was 13.7 for endocrine tumours, 12.9 for CNS tumours, 9.1 for pancreatic and 8.4 for head and neck cancer. For the four common cancers, the ratios were 4.9 (lung), 4.1 (colorectal), 2.6 (breast) and 2.6 (prostate). Conclusions: The risk of VTE in cancer patients is twice that of non-cancer patients; endocrine and CNS malignancies are strongly associated with symptomatic VTE.
4th Int. Conf. on Thrombosis and Hemostasis Issues in Cancer / Thrombosis Research 120 Suppl. 2 (2007) S145–S178
88% inhibition at 100 mg/mL. Migration was then visualized in a microfluidic system. When B-CLL cells were introduced in the device and CXCL12 was distributed uniformly throughout the chamber, cells migrated toward the higher concentration of CXCL12. On the contrary, when CXCL12 was preincubated with heparin before loading in the device, cells underwent chemokinesis or unbiased motion. Conclusions: Clinically relevant concentrations of nadroparin inhibit the CXCL12-driven chemotaxis of B-CLL cells. By sequestering CXCL12, nadroparin may affect interactions of leukemia cells with protective microenvironments. PO-59 Low molecular weight heparin (LMWH) versus best supportive care in cancer patients. A meta-analysis of randomized clinical trials S. Laporte1 *, G. Meyer2 , H.R. B¨ uller3 , H. Decousus1,4 , N. Moulin5 , M. Cucherat6 , P. Mismetti1,5 . 1 Dept of clinical pharmacology, EA3065, University Hospital of Saint-Etienne, France, 2 Dept of pulmonology, European Hospital Georges Pompidou, Paris, France, 3 Dept of vascular medicine, Academic Medical Center, Amsterdam, The Netherlands, 4 INSERM CIE3, EA3065, University Hospital of Saint-Etienne, France, 5 Dept. of internal medicine, EA3065, University Hospital of Saint-Etienne, France, 6 Dept of clinical pharmacology, University Hospital of Lyon, France Introduction: Several studies have suggested a possible antitumor effect of LMWH. Meta-analyses have been done but focusing either on VTE patients or on cancer patients free of VTE. In addition, results summarized death rates at a given time rather than survival data, involving a lost of information. Aim: We performed a meta-analysis of randomized clinical trials (RCTs) in cancer patients with or without VTE to assess the potential survival benefit of LMWH compared to best supportive care. Patients and Methods: Medline, Cancerlit, Embase, Google Scholar and Cochrane Library searches were supplemented by abstract of meetings (ASCO, ECCO, ISTH, ASH). We included all RCTs comparing LMWH to best supportive care, i.e. placebo or no treatment in cancer patients free of VTE and VKA in cancer patients with VTE. Hazard ratio (HR) and 95% CI of overall survival was computed with individual patient data when available, directly extracted from publication, or derived from the number of deaths, log-rank p-value or survival curve [Parmar M et al. Stat Med 1998]. Results: A total of 10 RCTs comparing LMWH to best supportive care were found, 6 versus placebo/no treatment in cancer patients free of VTE (912 patients; 2 trials pending), and 4 versus VKA in VTE patients (1120 patients). A significant 13% improvement of overall survival was found with LMWH (HR = 0.87 [0.78; 0.97], P = 0.02), without heterogeneity between trials in patients with or without VTE (P = 0.42). Conclusion: Compared to best supportive care, LMWH seem to increase overall survival in cancer patients. Meta-analysis on individual patient data could improve information regarding the type of cancer and presence of metastases. PO-60 Meta-analysis of randomised comparisons between the effects of warfarin and low molecular weight heparin in thromboprophylaxis and mortality in cancer patients A.M. Young *, L. Gross, R. Hills, K. Wheatley. University of Birmingham Clinical Trials Unit, Birmingham, England Introduction: The role of the low molecular weight heparins and warfarin in the prophylaxis of venous thromboembolism (VTE) in cancer patients remains uncertain. A meta-analysis was performed to determine the effects of warfarin and LMWH on primary and secondary VTE rates and mortality. Methods: Computerised searches in MedLine, NCI Trials Register, ISTH, ASCO and ASH proceedings and reference checks were carried out for papers from 1984 onwards, to Oct 2006. The inclusion criteria
set were: RCTs; medical cancer patients; thromboprophylaxis; warfarin or heparin vs no treatment or placebo or warfarin vs heparin. Standard meta-analysis methods were utilised and results were presented as ORs and CIs with tests for interaction used to determine heterogeneity of treatment effect. Results: 27 trials with 6,320 patients were found to match the criteria; this included thromboprophylaxis in patients with central venous catheters (CVCs); some cancer data were extracted for patients from all disease trials if possible. In 6 trials (n = 1,667) of warfarin vs not, there was no clear evidence of a decrease in VTEs (OR = 0.72, CI = 0.49 1.06, p = 0.09) A total of 9 trials (n = 2,621) had survival data: there was no clear benefit of a decrease in mortality with warfarin (OR = 0.92, CI = 0.82 1.02, p = 0.1). In 7 trials (n = 2,441) of LMWH vs not, VTE was reduced (OR = 0.62, CI = 0.44 0.89, p = 0.009). 5 trials (n = 1,211) contained survival data and mortality was reduced with LMWH (OR = 0.78, CI = 0.67 0.91 p = 0.002). In 8 trials of LMWH vs oral anticoagulation (mainly warfarin), (n = 1,179), VTE rates were less with LMWH (OR = 0.49 CI = 0.35 0.69, p 0.001). No mortality benefit was observed in 10 trials (n = 1,100) (OR = 0.95, CI = 0.80 1.14, p = 0.6). Conclusions: The results of these meta-analyses suggest that LMWH is the preferred form of prophylaxis for VTE in cancer patients and that overall, there may be an anti-tumour effect, leading to a survival benefit.
PO-61 Cancer and symptomatic venous thromboembolism rates: VERITY Registry findings P. Rose1 *, P. Shankara2 , A. McManus3 , Z. Lester4 , T. Nokes4 , T. Farren5 , N. Scriven6 , R. Arya7 , D. O’Shaughnessy8 , for the VERITY Investigators. 1 Warwick Hospital, Warwick; 2 Heart of England NHS Foundation Trust, Birmingham; 3 MMRx Research, London; 4 Derriford Hospital, Plymouth Hospitals NHS Trust; 5 Barts and the London Hospitals, London; 6 The Calderdale Royal Hospital, Halifax; 7 King’s College Hospital, London; 8 Department of Health, London, UK Introduction: VTE rates in specific cancers and its impact on mortality are poorly characterized. VERITY, an ongoing UK prospective VTE treatment registry, has enrolled ~70,000 patients with suspected or confirmed VTE, including >4,000 cancer patients. Aim: We compared VTE rates in cancer and non-cancer patients and the prevalence of different cancer types in VTE-positive and VTEnegative cases. Patients and methods: By July 2007, 69,661 patients had been enrolled. VTE diagnosis was known in 58,810 patients; 26.7% (n = 15,682) had confirmed VTE, 73.3% (n = 43,128) had a diagnosis of VTE excluded and 6.5% (n = 3,832) had cancer. Results: Cancer was >3 times more prevalent in the VTE population than the non-VTE patients 13.5% (2,116/15,682) vs. 4% (1716/43128), respectively. Comparing cancer to noncancer patients, VTE was 2-fold higher in cancer patients (55.2% [2,116/3,832] vs. 24.9% [13,566/54,474], respectively). The most common forms of cancer (breast, prostate, colorectal and lung) matched the cancers most commonly diagnosed with VTE (1,064 cases, or 50.3% of all cancer cases with VTE). However, calculating the ratio of the incidence of each cancer type in the VTE patients to the non-VTE patients offers a different insight into which cancers are particularly apparent in the VTE population. The ratio was 13.7 for endocrine tumours, 12.9 for CNS tumours, 9.1 for pancreatic and 8.4 for head and neck cancer. For the four common cancers, the ratios were 4.9 (lung), 4.1 (colorectal), 2.6 (breast) and 2.6 (prostate). Conclusions: The risk of VTE in cancer patients is twice that of non-cancer patients; endocrine and CNS malignancies are strongly associated with symptomatic VTE.