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Intervention Review

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Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation

  1. Elie A Akl1,*,
  2. Lara Kahale2,
  3. Irene Terrenato3,
  4. Ignacio Neumann4,
  5. Victor E D Yosuico5,
  6. Maddalena Barba6,
  7. Francesca Sperati3,
  8. Holger Schünemann7

Editorial Group: Cochrane Gynaecological Cancer Group

Published Online: 4 JUN 2014

Assessed as up-to-date: 9 FEB 2013

DOI: 10.1002/14651858.CD006466.pub4


How to Cite

Akl EA, Kahale L, Terrenato I, Neumann I, Yosuico VED, Barba M, Sperati F, Schünemann H. Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD006466. DOI: 10.1002/14651858.CD006466.pub4.

Author Information

  1. 1

    American University of Beirut, Department of Internal Medicine, Beirut, Lebanon

  2. 2

    American University of Beirut, Faculty of Medicine, Beirut, Lebanon

  3. 3

    Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome, Italy

  4. 4

    Faculty of Medicine, Pontificia Universidad Católica de Chile, Department of Internal Medicine, Evidence Based Health Care Program, Santiago, Región metropolitana, Chile

  5. 5

    State University of New York at Buffalo, Department of Medicine, Buffalo, NY, USA

  6. 6

    Regina Elena National Cancer Institute, Division of Medical Oncology B - Scientific Direction, Rome, Italy

  7. 7

    McMaster University, Departments of Clinical Epidemiology and Biostatistics and of Medicine, Hamilton, Ontario, Canada

*Elie A Akl, Department of Internal Medicine, American University of Beirut, Riad El Solh St, Beirut, Lebanon. ea32@aub.edu.lb.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 4 JUN 2014

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This is not the most recent version of the article. View current version (01 JUL 2014)

References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Chahinian 1989 {published data only}
  • Chahinian AP, Propert KJ, Ware JH, Zimmer B, Perry MC, Hirsh V, et al. A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. Journal of Clinical Oncology 1989;7(8):993-1002.
Daly 1991 {published data only}
Levine 1994 {published data only}
  • Levine M, Hirsh J, Gent M, Arnold A, Warr D, Falanga A, et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994;343(8902):886-9.
Levine 2012 {published data only}
  • Levine MN, Gu C, Liebman HA, Escalante CP, Solymoss S, Deitchman D, et al. A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer. Journal of Thrombosis and Haemostasis 2012;10:807-14.
  • Liebman H, Levine MN, Deitchman D, Julian J, Escalante CP, O'Brien MC, et al. Apixaban in patients with metastatic cancer: a randomized phase II feasibility study. XXII Congress of the International Society on Thrombosis and Haemostasis. 2009:PP-WE-489.
Maurer 1997 {published data only}
  • Maurer LH, Herndon IJ, Hollis DR, Aisner J, Carey RW, Skarin AT, et al. Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study. Journal of Clinical Oncology 1997;15(11):3378-87.
Stanford 1979 {published data only}
Zacharski 1984 {published data only}
  • Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ Jr, Forcier RJ, et al. Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75. Cancer 1984;53(10):2046-52.
  • Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ Jr, Forcier RJ, et al. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans administration study No. 75. 1981 JAMA;245(8):831-5.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Aisner 1987 {published data only}
  • Aisner J, Propert K. Aggressive combination chemotherapy, chest and brain irradiation and warfarin for the treatment of limited disease of small cell lung cancer (SCLC). Proceedings of the American Society of Clinical Oncology 1987;6:179.
Aisner 1992 {published data only}
  • Aisner J, Goutsou M, Maurer LH, Cooper R, Chahinian P, Carey R, et al. Intensive combination chemotherapy, concurrent chest irradiation, and warfarin for the treatment of limited-disease small-cell lung cancer: a Cancer and Leukemia Group B pilot study. Journal of Clinical Oncology 1992;10(8):1230-6.
Anonymous 1994 {published data only}
  • Anonymous. Coumarin (1,2-benzopyrone) - new findings for tumor therapy. Medizinische Welt 1994;45(5):62-3.
Carpi 1995 {published data only}
  • Carpi A, Sagripanti A, Poddighe R, Gherarducci G, Nicolini A. Cancer incidence and mortality in patients with heart disease. Effect of oral anticoagulant therapy. American Journal of Clinical Oncology 1995;18(1):15-8.
Chahinian 1984 {published data only}
  • Chahinian AP, Ware JH, Zimmer B, Comis RL, Perry MC, Hirsh V, et al. Evaluation of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer (SCCL). Proceedings of the American Society of Clinical Oncology 1984:C-879.
Chahinian 1985 {published data only}
  • Chahinian AP, Ware JH, Zimmer B, Comis RL, Perry MC, Hirsh V, et al. Update on anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer (SCCL). Proceedings of the American Society of Clinical Oncology 1985;4:191.
Chlebowski 1982 {published data only}
  • Chlebowski RT, Gota CH, Chan KK, Weiner JM, Block JB, Bateman JR. Clinical and pharmacokinetic effects of combined warfarin and 5-fluorouracil in advanced colon cancer. Cancer Research 1982;42(11):4827-30.
D'Souza 1980a {published data only}
  • D'Souza DP, Daly L, Thornes RD. Low dosage chemoimmunotherapy plus warfarin in metastatic breast cancer. Irish Journal of Medical Science 1980;149(4):172-3.
D'Souza 1980b {published data only}
  • D'Souza DP, Daly L, Thornes RD. Cyclophosphamide, prednisone, staphage lysate and warfarin in disseminated breast cancer. Irish Medical Journal 1980;73(10):385-7.
Demir 2006 {published data only}
  • Demir M, Hoppensteadt DA, Cunanan J, Iqbal O, Fareed J. Increased levels of inflammatory mediators in lung cancer and their modulation by oral anticoagulant treatment. Journal of Clinical Oncology, ASCO Annual Meeting Proceedings. Post-Meeting edition 2006;24:18S.
Demir 2007 {published data only}
  • Demir M, Ciftci A, Hoppensteadt D, Altiay G, Tobu M, Iqbal O, et al. Protein chip array profiling and markers of inflammation and thrombin generation in plasma samples from lung cancer patients and their modulation by chemotherapy with or without warfarin anticoagulation. Journal of Clinical Oncology, ASCO Annual Meeting Proceedings. 2007.
Herrmann 1988 {published data only}
  • Herrmann R. Coumarin and cimetidine in the treatment of metastatic renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 1988;7:131.
Herrmann 1990 {published data only}
  • Herrmann R, Manegold C, Maurer B, Hennig FW, Matthiessen W. Phase II trial of coumarin and cimetidine in advanced renal cell carcinoma. Annals of Oncology 1990;1(6):445-6.
Higashi 1971 {published data only}
  • Higashi H, Heidelberger C. Lack of effect of warfarin (NSC-59813) alone or in combination with 5-fluorouracil (NSC-19893) on primary and metastatic L1210 leukemia and adenocarcinoma 755. Cancer Chemotherapy Reports - Part 1 1971;55(1):29-33.
Hoppensteadt 2011 {published data only}
  • Hoppensteadt D, Khan H, Thethi I, Demir M, Adiguzel C, Rahman S, et al. Inflammatory and thrombotic mediators in small cell lung carcinoma: potential role in thromboembolic complications. American Society of Hematology, Annual Meetings and Exposition 2294. 2011.
Huber 1993 {published data only}
Hutchins 1984 {published data only}
  • Hutchins LF, Cash DK, Lang NP, Neilan BA. Coumarin and cimetidine as active agents in melanoma and renal-cell carcinoma. Clinical Research 1984;32(5):A873.
Khan 2012 {published data only}
  • Khan H, Thethi I, Hoppensteadt D, Demir M, Adiguzel C, Rahman S, et al. Inflammatory and thrombotic mediators in small cell lung carcinoma: potential role in thromboembolic complications. Hamostaseologie 2012:P10-2.
Kokron 1990 {published data only}
  • Kokron O, Baumgartner G, Theyer G, Maca S, Gasser G, Schmidt PR, et al. Cimetidine and coumarin treatment of metastatic renal cell carcinoma. Journal of Cancer Research & Clinical Oncology 1990;116(Suppl):971.
Kokron 1993 {published data only}
  • Kokron O, Baumgartner G, Theyer G, Maca S, Gasser G, Schmidt PR, et al. Randomised study in metastatic renal cell cancer: coumarin versus coumarin and cimetidine. Journal of the Irish Colleges of Physicians & Surgeons 1993;22 Suppl 1:10-1.
Lebeau 1993 {published data only}
  • Lebeau B, Chastang C, Muir JF, Vincent J, Massin F, Fabre C. No effect of an antiaggregant treatment with aspirin in small-cell lung-cancer treated with Ccavp16 chemotherapy - results from a randomized clinical-trial of 303 patients. Cancer 1993;71(5):1741-5.
Lecumberri 2005 {published data only}
  • Lecumberri R, Paramo JA, Rocha E. Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies. Haematologica 2005;90(9):1258-66.
Loprinzi 1999 {published data only}
  • Loprinzi C, Kugler J, Sloan J, Rooke T, Quella S, Novotny P, et al. Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. New England Journal of Medicine 1999;340:346-50.
Macareo 2001 {published data only}
  • Macareo LR, Ford SM, Crocker JD, Coleman TA. Low dose warfarin decreases central line thrombosis and tissue plasminogen activator (TPA) utilization in cancer patients but does not improve overall survival. Blood 2001;98(11):94B-5B.
Marshall 1987 {published data only}
  • Marshall ME, Mendelsohn L, Butler K, Cantrell J, Harvey J, Macdonald J. Treatment of non-small cell lung cancer with coumarin and cimetidine. Cancer Treatment Reports 1987;71(1):91-2.
Marshall 1989 {published data only}
  • Marshall ME, Butler K, Cantrell J, Wiseman C, Mendelsohn L. Treatment of advanced malignant melanoma with coumarin and cimetidine: a pilot study. Cancer Chemotherapy & Pharmacology 1989;24(1):65-6.
Marshall 1990 {published data only}
  • Marshall FF. Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma: editorial comment. Journal of Urology 1990;144(5):1317.
McCulloch 1987 {published data only}
Moazzam 2003 {published data only}
  • Moazzam N, Potti A. Survival and outcome data in patients with adenocarcinoma of the prostate receiving warfarin therapy. Blood 2003;102(11):325A.
Mohler 1993 {published data only}
  • Mohler JL, Williams B, Thompson I, Marshall ME. Coumarin (1,2-benzopyrone) for the treatment of prostatic carcinoma. Journal of the Irish Colleges of Physicians & Surgeons 1993;22 Suppl 1:12-6.
Mohler 1994 {published data only}
Sagaster 1995 {published data only}
  • Sagaster P, Micksche M, Flamm J, Ludwig H. Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Annals of Oncology 1995;6(10):999-1003.
Smorenburg 2001 {published data only}
  • Smorenburg SM, Van Noorden CJ. The complex effects of heparins on cancer progression and metastasis in experimental studies. Pharmacological Review 2001;53(1):93-105.
Taliani 2003 {published data only}
Taliani 2004 {published data only}
Thethi 2011 {published data only}
  • Thethi I, Hoppensteadt D, Khan H, Demir M, Adiguzel C, Litinas E, et al. Procoagulant and inflammatory mediators in small cell lung carcinoma: potential role in thromboembolic complications. Journal of Clinical Oncology 2011;29 Suppl:2553.
Thornes 1972 {published data only}
  • Thornes RD. Warfarin as maintenance therapy for cancer. Journal of the Irish Colleges of Physicians and Surgeons 1972;29(2):41-2.
Thornes 1974 {published data only}
Thornes 1975 {published data only}
Thornes 1984 {published data only}
  • Thornes RD. Prevention of recurrence of kaposis sarcoma, breast-cancer and melanoma by coumarin. Irish Journal of Medical Science 1984;153(5):187.
Thornes 1989 {published data only}
  • Thornes D, Daly L, Lynch G, Browne H, Tanner A, Keane, et al. Prevention of early recurrence of high risk malignant melanoma by coumarin. European Journal of Surgical Oncology 1989;15(5):431-5.
Thornes 1993 {published data only}
  • Thornes RD. Prevention of recurrence of malignant melanoma by coumarin (1,2-benzopyrone). Journal of the Irish Colleges of Physicians & Surgeons 1993;22 Suppl 1:17-9.
Thornes 1994 {published data only}
  • Thornes RD, Daly L, Lynch G, Breslin B, Browne H, Browne HY, et al. Treatment with coumarin to prevent or delay recurrence of malignant melanoma. Journal of Cancer Research & Clinical Oncology 1994;120 Suppl:S32-4.
Tiska-Rudman 2001 {published data only}
  • Tiska-Rudman L, Stamenic V, Rudman Jr F, Zekaj S, Sabol R. Ten-year survival in patients receiving anticoagulant therapy for breast cancer. Libri Oncologici 2001;29(2):99-108.
Venook 1989 {published data only}
Zacharski 1979 {published data only}
  • Zacharski LR. Clinical trial of warfarin in cancer. Thrombosis & Haemostasis 1979;42(1):xx.
Zacharski 1982a {published data only}
  • Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ, Forcier RJ, et al. Effect of warfarin therapy on survival in cancer - final report of VA Cooperative Study #75. Circulation 1982;66(4):302.
Zacharski 1982b {published data only}
Zacharski 1990 {published data only}
Zacharski 1993 {published data only}
  • Zacharski LR. Warfarin therapy for cancer. Journal of the Irish Colleges of Physicians & Surgeons 1993;22 Suppl 1:20-3.
Zacharski 2002 {published data only}

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Bristol-Myers Squibb 2006 {published data only}
  • A Randomized, Double-blind, Placebo-controlled Study of Apixaban for the Prevention of Thromboembolic Events in Patients Undergoing Treatment for Advanced Cancer: a Phase 2 Pilot Study. Ongoing study June 2006.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Akl 2010
Akl 2011
  • Akl EA, Gunukula S, Barba M, Yosuico VE, van Doormaal FF, Kuipers S, et al. Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database of Systematic Reviews 2011, Issue 1. [DOI: 10.1002/14651858.CD006652.pub3]
Akl 2013
  • Akl EA, Johnston BC, Alonso-Coello P, Neumann I, Ebrahim S, Briel M, et al. Addressing dichotomous data for participants excluded from trial analysis: a guide for systematic reviewers. PLoS One 2013;8(2):e57132.
Ansell 2008
  • Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):160S-98S.
Deeks 2001
  • Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Egger M, Davey Smith G, Altman DG editor(s). Systematic Reviews in Health Care: Meta-Analysis in Context. 2nd Edition. London: BMJ Publication Group, 2001.
Dvorak 1986
Ebrahim 2013
  • Ebrahim S, Akl EA, Mustafa RA, Sun X, Walter SD, Heels-Ansdell D, et al. Addressing continuous data for participants excluded from trial analysis: a guide for systematic reviewers. Journal of Clinical Epidemiology 2013;66(9):1014-21.
Francis 1998
Higgins 2003
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
King 2013
Levine 2003
Miller 2004
Schulman 2000
  • Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial. New England Journal of Medicine 2000;342(26):1953-8.
Zacharski 1981
  • Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ Jr, Forcier RJ, et al. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. 1981 JAMA;245(8):831-5.
Zhang 2013
  • Zhang J, Zhang YL, Ma KX, Qu JM. Efficacy and safety of adjunctive anticoagulation in patients with lung cancer without indication for anticoagulants: a systematic review and meta-analysis. Thorax 2013;68(5):442-50.