 |
 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
7 March 2000 | Volume 132 Issue 5 | Pages 364-368
Background: Thrombocytopenia is a significant problem in the treatment of cancer.
Objective: To assess the clinical safety of therapy with recombinant human thrombopoietin (rhTPO) and its ability to ameliorate chemotherapy-induced severe thrombocytopenia.
Design: Phase I/II clinical cohort study.
Setting: The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Patients: 29 patients with gynecologic cancer.
Intervention: Recombinant human thrombopoietin was given before chemotherapy and after a second cycle of carboplatin therapy.
Measurements: Peripheral blood counts and platelet transfusions.
Results: Administration of rhTPO after chemotherapy significantly reduced the degree and duration of thrombocytopenia and enhanced platelet recovery. In patients who received the optimal biological dose of rhTPO (1.2 µg/kg of body weight) in cycle 2 (carboplatin plus rhTPO), the mean platelet count nadir was higher (44 x 109 cells/L and 20 x 109 cells/L; P = 0.002) and the duration of thrombocytopenia was shorter (days with a platelet count <20 x 109 cells/L, 1 and 4 [P = 0.002]; days with a platelet count <50 x 109 cells/L, 4 and 7 [P = 0.006]) than in cycle 1 (carboplatin only). The need for platelet transfusion in this group was reduced from 75% of patients in cycle 1 to 25% of patients in cycle 2 (P = 0.013).
Conclusions: Therapy with rhTPO seems to be safe and may attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions.
Author and Article Information
From University of Texas M.D. Anderson Cancer Center, Houston, Texas; Indiana University School of Medicine, Indianapolis, Indiana; and Genentech, Inc., South San Francisco, California.
Acknowledgments: The authors thank Walter Hittelman, PhD, for critical review of the manuscript; Dennis A. Johnston, PhD, for statistical advice; Laura McGarry, RN, Timothy A. Yang, BA, and Virginia E. Paton, PharmD, for monitoring the study; and Carmelita Concepcion for manuscript preparation.
Grant Support: In part by National Institutes of Health grants RO1 HL56416, RO1 HL54037, and PO1 HL53586 and by a research grant from Genentech, Inc.
Requests for Single Reprints: Saroj Vadhan-Raj, MD, Department of Bioimmunotherapy, Box 002, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030; e-mail, svadhanr{at}notes.mdacc.tmc.edu.
Requests To Purchase Bulk Reprints (minimum, 100 copies): Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.
Current Author Addresses: Dr. Vadhan-Raj: Department of Bioimmunotherapy, Box 002, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Drs. Verschraegen, Kudelka, and Kavanagh: Gynecologic Medical Oncology, Box 039, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Dr. Bueso-Ramos: Laboratory Medicine-Patient Care Services, Box 072, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Drs. Freedman and Gershenson: Gynecologic Oncology, Box 067, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Dr. Edwards: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Baylor College of Medicine, Smith Tower, 6550 Fannin, Suite 701A, Houston, TX 77030.
Dr. Jones: Division of Hematology/Oncology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0565.
Dr. Ashby: Oncology Center/Medical Affairs, Genentech, Inc., Mailstop 59, 1 DNA Way, South San Francisco, CA 94080.
Author Contributions: Conception and design: S. Vadhan-Raj, C.F. Verschraegen, A.P. Kudelka, D.V. Jones, M. Ashby, J.J. Kavanagh.
Analysis and interpretation of the data: S. Vadhan-Raj, C. Bueso-Ramos, H.E. Broxmeyer, R.S. Freedman, C.L. Edwards, D. Gershenson, D.V. Jones, M. Ashby, J.J. Kavanagh.
Drafting of the article: S. Vadhan-Raj.
Critical revision of the article for important intellectual content: S. Vadhan-Raj, C.F. Verschraegen, C. Bueso-Ramos, H.E. Broxmeyer, A.P. Kudelka, R.S. Freedman, C.L. Edwards, D. Gershenson, M. Ashby, J.J. Kavanagh.
Final approval of the article: S. Vadhan-Raj, C.F. Verschraegen, C. Bueso-Ramos, H.E. Broxmeyer, A.P. Kudelka, R.S. Freedman, D. Gershenson, M. Ashby, J.J. Kavanagh.
Provision of study materials or patients: S. Vadhan-Raj, C.F. Verschraegen, A.P. Kudelka, R.S. Freedman, C.L. Edwards, D. Gershenson, D.V. Jones, J.J. Kavanagh.
Statistical expertise: M. Ashby.
Obtaining of funding: S. Vadhan-Raj, D.V. Jones.
Administrative, technical, or logistic support: S. Vadhan-Raj.
Collection and assembly of data: S. Vadhan-Raj, H.E. Broxmeyer, D.V. Jones. BRIEF COMMUNICATION
Recombinant Human Thrombopoietin Attenuates Carboplatin-Induced Severe Thrombocytopenia and the Need for Platelet Transfusions in Patients with Gynecologic Cancer
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  H. Takedatsu, K. Yoshimoto, T. Okamura, H. Miyazaki, T. Kuwaki, M. Sata, and K. Itoh Determination of Thrombopoietin-Derived Peptides Recognized by Both Cellular and Humoral Immunities in Healthy Donors and Patients with Thrombocytopenia Stem Cells, August 1, 2005; 23(7): 975 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Angiolillo, V. Davenport, M. A. Bonilla, C. van de Ven, J. Ayello, O. Militano, L. L. Miller, M. Krailo, G. Reaman, and M. S. Cairo A Phase I Clinical, Pharmacologic, and Biologic Study of Thrombopoietin and Granulocyte Colony-Stimulating Factor in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Recurrent or Refractory Solid Tumors: A Children's Oncology Group Experience Clin. Cancer Res., April 1, 2005; 11(7): 2644 - 2650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Farese, T. J. MacVittie, L. Roskos, and R. B. Stead Hematopoietic Recovery Following Autologous Bone Marrow Transplantation in a Nonhuman Primate: Effect of Variation in Treatment Schedule with PEG-rHuMGDF Stem Cells, January 1, 2003; 21(1): 79 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kuter and C. G. Begley Recombinant human thrombopoietin: basic biology and evaluation of clinical studies Blood, November 15, 2002; 100(10): 3457 - 3469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Linden and K. Kaushansky The Glycan Domain of Thrombopoietin (TPO) Acts in trans to Enhance Secretion of the Hormone and Other Cytokines J. Biol. Chem., September 13, 2002; 277(38): 35240 - 35247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, C. Yang, Y. Xia, A. Bertino, J. Glaspy, M. Roberts, and D. J. Kuter Thrombocytopenia caused by the development of antibodies to thrombopoietin Blood, December 1, 2001; 98(12): 3241 - 3248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Demetri Targeted Approaches for the Treatment of Thrombocytopenia Oncologist, October 1, 2001; 6(2008): 15 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Kuter, L. T. Goodnough, J. Romo, J. DiPersio, R. Peterson, D. Tomita, W. Sheridan, and J. McCullough Thrombopoietin therapy increases platelet yields in healthy platelet donors Blood, September 1, 2001; 98(5): 1339 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. Goodnough, D. J. Kuter, J. McCullough, S. J. Slichter, J. DiPersio, J. Romo, R. Peterson, K. J. Smith, T. Raife, D. Tomita, et al. Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin Blood, September 1, 2001; 98(5): 1346 - 1351. [Abstract] [Full Text] [PDF]
|
|
Article
