Adverse Effects of Drugs Used to Treat Hematologic Malignancies: Surveillance Efforts from the Research on Adverse Drug Events and Reports Project

 

 Buy Article Permissions and Reprints

ABSTRACT

Pharmaceuticals used to treat hematologic malignancies can lead to unexpected adverse events that involve a wide range of organ systems and physiological processes. The National Cancer Institute and National Heart Lung and Blood Institute-funded Research on Adverse Drug Events and Reports (RADAR) project-a collaboration of the Robert H. Lurie Comprehensive Cancer Center, the Department of Veterans Affairs, the Northwestern University Feinberg School of Medicine, and numerous academic institutions-identifies and evaluates unexpected adverse drug reactions associated with drugs used to treat malignant disorders. This article reviews the features of the safety program maintained by the U.S. Food and Drug Administration and the RADAR program.

REFERENCES

• 1 Lazarou J, Pomeranz B H, Corey P N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.  JAMA. 1998;  279(15) 1200-1205
  Google Scholar
• 2 Ladewski L A, Belknap S M, Nebeker J R et al.. Dissemination of information on potentially fatal adverse drug reactions for cancer drugs from 2000 to 2002: first results from the research on adverse drug events and reports project.  J Clin Oncol. 2003;  21(20) 3859-3866
  CrossrefPubMedGoogle Scholar
• 3 Lasser K E, Seger D L, Yu D T et al.. Adherence to black box warnings for prescription medications in outpatients.  Arch Intern Med. 2006;  166(3) 338-344
  CrossrefPubMedGoogle Scholar
• 4 Fast Track . Accelerated approval and priority review: accelerating availability of new drugs for patients with serious diseases.  U.S. Food and Drug Administration. May 2006;  http://www.fda.gov/oashi/fast.html#accelerated , Accessed November 27, 2006
  PubMedGoogle Scholar
• 5 Trontell A. Expecting the unexpected-drug safety, pharmacovigilance, and the prepared mind.  N Engl J Med. 2004;  351(14) 1385-1387
  CrossrefPubMedGoogle Scholar
• 6 Smalley W, Shatin D, Wysowski D K et al.. Contraindicated use of cisapride: impact of food and drug administration regulatory action.  JAMA. 2000;  284(23) 3036-3039
  CrossrefPubMedGoogle Scholar
• 7 Basser R L, O'Flaherty E, Green M et al.. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor.  Blood. 2002;  99(7) 2599-2602
  CrossrefPubMedGoogle Scholar
• 8 Graf G, Zaborski M, Quentmeier H, Drexler H G. Phorbol ester PMA induces expression of the thrombopoietin receptor MPL in leukemia cells.  Leuk Lymphoma. 1996;  24(1-2) 149-157
  PubMedGoogle Scholar
• 9 Kessler D A. Introducing MEDWatch. A new approach to reporting medication and device adverse effects and product problems.  JAMA. 1993;  269(21) 2765-2768
  CrossrefPubMedGoogle Scholar
• 10 Almenoff J, Tonning J M, Gould A L et al.. Perspectives on the use of data mining in pharmaco-vigilance.  Drug Saf. 2005;  28(11) 981-1007
  CrossrefPubMedGoogle Scholar
• 11 Sargent D J, Goldberg R M, Mahoney M R et al.. Rapid reporting and review of an increased incidence of a known adverse event.  J Natl Cancer Inst. 2000;  92(12) 1011-1013
  CrossrefPubMedGoogle Scholar
• 12 Soares H, Kumar A, Djulbegovic B. Quality of reporting of harms in NCI sponsored phase III hematological malignancies trials.  Blood. 2005;  106 , (abst 292)
  PubMedGoogle Scholar
• 13 Bennett C L, Nebeker J R, Lyons E A et al.. The Research on Adverse Drug Events and Reports (RADAR) project.  JAMA. 2005;  293(17) 2131-2140
  CrossrefPubMedGoogle Scholar
• 14 Bennett C L, Luminari S, Nissenson A R et al.. Pure red-cell aplasia and epoetin therapy.  N Engl J Med. 2004;  351(14) 1403-1408
  CrossrefPubMedGoogle Scholar
• 15 Bennett C L, Connors J M, Carwile J M et al.. Thrombotic thrombocytopenic purpura associated with clopidogrel.  N Engl J Med. 2000;  342(24) 1773-1777
  CrossrefPubMedGoogle Scholar
• 16 Rajvanshi P, Shulman H M, Sievers E L, McDonald G B. Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy.  Blood. 2002;  99(7) 2310-2314
  CrossrefPubMedGoogle Scholar
• 17 Wadleigh M, Richardson P G, Zahrieh D et al.. Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation.  Blood. 2003;  102(5) 1578-1582
  CrossrefPubMedGoogle Scholar
• 18 Cohen A D, Luger S M, Sickles C et al.. Gemtuzumab ozogamicin (Mylotarg) monotherapy for relapsed AML after hematopoietic stem cell transplant: efficacy and incidence of hepatic veno-occlusive disease.  Bone Marrow Transplant. 2002;  30(1) 23-28
  CrossrefPubMedGoogle Scholar
• 19 McKoy J M, Angelotta C, Bennett C L et al.. Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project.  Leuk Res. 2006 (September);  7 , (Epub ahead of print)
  PubMedGoogle Scholar
• 20 Bennett C L, Angelotta C, Yarnold P R et al.. Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer.  JAMA. 2006;  296(21) 2558-2560
  PubMedGoogle Scholar
• 21 Dimopoulos M, Spencer A, Atfal M et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010).  Blood. 2005;  106 , (abst 6)
  PubMedGoogle Scholar
• 22 Food and Drug Administration . Lenalidomide package insert.  Available at: http://www.fda.gov/cder/foi/label/2006/021880s001.pdf , Accessed September 6, 2006
  Google Scholar
• 23 Food and Drug Administration . Thalidomide package insert.  Available at: http://www.fda.gov/cder/foi/label/2006/021430s000,020785s031lbl.pdf , Accessed September 6, 2006
  Google Scholar
• 24 Bennett C L, Schumock G T, Desai A A et al.. Thalidomide-associated deep vein thrombosis and pulmonary embolism.  Am J Med. 2002;  113(7) 603-606
  CrossrefPubMedGoogle Scholar
• 25 Knight R, DeLap R J, Zeldis J B. Lenalidomide and venous thrombosis in multiple myeloma.  N Engl J Med. 2006;  354(19) 2079-2080
  CrossrefPubMedGoogle Scholar
• 26 Rajkumar S V, Blood E. Lenalidomide and venous thrombosis in multiple myeloma.  N Engl J Med. 2006;  354(19) 2079-2080
  CrossrefPubMedGoogle Scholar
• 27 Zonder J A, Barlogie B, Durie B G, McCoy J, Crowley J, Hussein M A. Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis.  Blood. 2006;  108(1) 403 , (author reply 404)
  CrossrefPubMedGoogle Scholar
• 28 Leyland-Jones B. Breast cancer trial with erythropoietin terminated unexpectedly.  Lancet Oncol. 2003;  4(8) 459-460
  CrossrefPubMedGoogle Scholar
• 29 Henke M, Laszig R, Rube C et al.. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial.  Lancet. 2003;  362(9392) 1255-1260
  CrossrefPubMedGoogle Scholar
• 30 Lasser K E, Allen P D, Woolhandler S J, Himmelstein D U, Wolfe S M, Bor D H. Timing of new black box warnings and withdrawals for prescription medications.  JAMA. 2002;  287(17) 2215-2220
  CrossrefPubMedGoogle Scholar
• 31 Trontell A E. The RADAR project and the FDA.  JAMA. 2005;  294(10) 1206 , (author reply 1206-1207)
  PubMedGoogle Scholar
• 32 Waxman H A. The lessons of Vioxx-drug safety and sales.  N Engl J Med. 2005;  352(25) 2576-2578
  CrossrefPubMedGoogle Scholar

Dr. Charles L Bennett

Northwestern University, 303 E. Chicago Avenue, Olson Pavilion

Suite 8250, Chicago, IL 60611

Email: cbenne@northwestern.edu