This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Basser, R. L. Articles by Begley, C. G. Search for Related Content PubMed PubMed Citation Articles by Basser, R. L. Articles by Begley, C. G.

Enhancement of Platelet Recovery After Myelosuppressive Chemotherapy by Recombinant Human Megakaryocyte Growth and Development Factor in Patients With Advanced Cancer

From the Centre for Developmental Cancer Therapeutics, Parkville; Amgen Australia, Kew, Victoria, Australia; and Amgen, Inc, Thousand Oaks, CA. See Appendix for a list of the affiliates of the Centre for Developmental Cancer Therapeutics.

Address reprint requests to R. Basser, MD, CDCT, c/o Post Office, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; email russell.basser{at}nwhcn.org.au

PURPOSE: To explore the influence of dose and schedule on the ability of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) to abrogate thrombocytopenia after multiple cycles of chemotherapy and to mobilize peripheral-blood progenitor cells (PBPC).

PATIENTS AND METHODS: In this open-label study, 68 patients with advanced cancer were randomized to receive PEG-rHuMGDF subcutaneously at different doses and durations before administration of carboplatin 600 mg/m², cyclophosphamide 1,200 mg/m², and filgrastim 5 µg/kg/d. PEG-rHuMGDF was not given after the first cycle of chemotherapy but was given after the second and subsequent cycles. Chemotherapy was given every 28 days for up to six cycles.

RESULTS: In patients who received the same dose of chemotherapy for at least two cycles, the platelet nadir was significantly higher (47.5 x 10⁹/L v 35.5 x 10⁹/L; P = .003) and duration of grade 3 or 4 thrombocytopenia significantly shorter (0 v 3 days; P = .004) when PEG-rHuMGDF was administered after chemotherapy. There was no evidence of an effect of PEG-rHuMGDF when it was given before chemotherapy. Platelet recovery after the first cycle of chemotherapy was no different for different PEG-rHuMGDF regimens, and there was no difference between patients treated with PEG-rHuMGDF and historical controls treated with identical chemotherapy. There was a modest dose-related increase in progenitor cell levels after administration of PEG-rHuMGDF alone. Peak levels of PBPC occurred later in cycle 2 than in cycle 1 but were not different in magnitude.

CONCLUSION: PEG-rHuMGDF abrogated severe thrombocytopenia after dose-intensive chemotherapy. However, it had only a modest effect on progenitor cell levels and did not enhance progenitor cell mobilization after chemotherapy and filgrastim.

This article has been cited by other articles:

				D. J. Kuter New thrombopoietic growth factors Blood, June 1, 2007; 109(11): 4607 - 4616. [Abstract] [Full Text] [PDF]

				B. Andemariam, B. Psaila, and J. B. Bussel Novel Thrombopoietic Agents Hematology, January 1, 2007; 2007(1): 106 - 113. [Abstract] [Full Text] [PDF]

				D. H. Gunawardana, R. L. Basser, I. D. Davis, J. Cebon, P. Mitchell, C. Underhill, T. J. Kilpatrick, K. Reardon, M. D. Green, P. Bardy, et al. A Phase I Study of Recombinant Human Leukemia Inhibitory Factor in Patients with Advanced Cancer Clin. Cancer Res., June 1, 2003; 9(6): 2056 - 2065. [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]

				R. L. Basser, E. O'Flaherty, M. Green, M. Edmonds, J. Nichol, D. M. Menchaca, B. Cohen, and C. G. Begley Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor Blood, April 1, 2002; 99(7): 2599 - 2602. [Abstract] [Full Text] [PDF]