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

Saroj Vadhan-Raj, MD; Claire F. Verschraegen, MD; Carlos Bueso-Ramos, MD; Hal E. Broxmeyer, PhD; Andrzej P. Kudelka, MD; Ralph S. Freedman, MD, PhD; Creighton L. Edwards, MD; David Gershenson, MD; Dennie Jones, MD; Mark Ashby, PhD; and John J. Kavanagh, MD
[+] Article and Author 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@notes.mdacc.tmc.edu.

Requests To Purchase Bulk Reprints (minimum, 100 copies): Reprints Coordinator; phone, 215-351-2657; e-mail, reprints@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.


Ann Intern Med. 2000;132(5):364-368. doi:10.7326/0003-4819-132-5-200003070-00005
Text Size: A A A

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.

Figures

Grahic Jump Location
Figure.
Platelet counts after therapy with recombinant human thrombopoietin (1.2 µg/kg administered on days 2, 4, 6, and 8) used as secondary prophylaxis after carboplatin treatment (cycle 2) (solid line) compared with those obtained by using carboplatin treatment alone (cycle 1) (dotted line).arrowheadsstars99

Each panel shows the kinetics of platelet count nadir and recovery in six patients who received recombinant human thrombopoetin. Among the five patients who required platelet transfusion ( ) in cycle 1, the need for platelet transfusion ( ) was eliminated in three and was reduced in one patient in cycle 2. The upper dashed line indicates a platelet count of 100 × 10 cells/L, and the lower dashed line indicates a platelet count of 20 × 10 cells/L.

Grahic Jump Location

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Summary for Patients

Thrombopoietin Is a Platelet Growth Factor That May Lessen the Need for Platelet Transfusions after Chemotherapy for Cancer

The summary below is from the full report titled “Recombinant Human Thrombopoietin Attenuates Carboplatin-Induced Severe Thrombocytopenia and the Need for Platelet Transfusions in Patients with Gynecologic Cancer.”. It is in the 7 March 2000 issue of Annals of Internal Medicine (volume 132, pages 364-368). The authors are S. Vadhan-Raj, C.F. Verschraegen, C. Bueso-Ramos, H.E. Broxmeyer, A.P. Kudelka, R.S. Freedman, C.L. Edwards, D. Gershenson, D. Jones, M. Ashby, and J.J. Kavanagh.

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