Preclinical pharmacologic basis for clinical use of rhIL-11 as an effective platelet-support agent.
Preclinical studies have shown that rhIL-11, also known as oprelvekin (Neumega), stimulates early and later stages of megakaryocytopoiesis (including proliferation and differentiation of megakaryocyte precursors and maturation of megakaryocytes), to produce an increase in peripheral platelet count. Because of these effects, rhIL-11 must be administered to patients with cancer sufficiently in advance of the platelet nadir (within 6 to 24 hours postchemotherapy) to allow adequate time for megakaryocyte maturation and platelet formation. Therefore, the maximum platelet response coincides with the time when the platelet nadir would normally be experienced. In myelosuppressed, nonhuman primates, optimal platelet response occurred following 14 days of treatment at a dose equivalent to the 50-microgram/kg daily dose recommended in humans; lower doses and shorter durations were less effective. These data support the current dosing recommendation in humans, which states that rhIL-11 dosing continues until platelet recovery to > or = 50,000/microL has been achieved for 2 consecutive days or for a total of 10 to 21 days in each cycle. The nonhematopoietic effects of rhIL-11 include a renal effect, resulting in plasma-volume expansion, as well as potential beneficial clinical effects in damaged or inflamed intestinal mucosa, including potential mitigation of mucositis and a rationale for future studies in inflammatory bowel disease.
Berl
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Department of Medicine, University of Colorado, Health Sciences Center, Denver, USA. Tomas.Berl@uchsc.edu
Schwertschlag
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology* / Q000502:physiology; D008252:Macaca fascicularis; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D023421:Models, Animal; D009092:Mucous Membrane / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000970:Antineoplastic Agents; D003115:Colony-Stimulating Factors; D017370:Interleukin-11; D011994:Recombinant Proteins; C105308:oprelvekin