Recombinant Human Thrombopoietin Attenuates Carboplatin-Induced Severe Thrombocytopenia and the Need for Platelet Transfusions in Patients with Gynecologic Cancer

  1. Saroj Vadhan-Raj, MD;
  2. Claire F. Verschraegen, MD;
  3. Carlos Bueso-Ramos, MD;
  4. Hal E. Broxmeyer, PhD;
  5. Andrzej P. Kudelka, MD;
  6. Ralph S. Freedman, MD, PhD;
  7. Creighton L. Edwards, MD;
  8. David Gershenson, MD;
  9. Dennie Jones, MD;
  10. Mark Ashby, PhD; and
  11. John J. Kavanagh, MD
  1. 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.

    Abstract

    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 × 109 cells/L and 20 × 109 cells/L; P = 0.002) and the duration of thrombocytopenia was shorter (days with a platelet count <20 × 109 cells/L, 1 and 4 [P = 0.002]; days with a platelet count <50 × 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.

    Article and Author Information

    • 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.

    Summary for Patients

    • Summaries for Patients:Thrombopoietin Is a Platelet Growth Factor That May Lessen the Need for Platelet Transfusions after Chemotherapy for Cancer Ann Intern Med March 7, 2000 132:364
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    1. Ann Intern Med March 7, 2000 vol. 132 no. 5 364-368
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