Recombinant human thrombopoietin clinical development

• Published in: Stem cells (Dayton, Ohio) Vol. 16; no. S1; pp. 199 - 206
• Main Authors: Jones, Dennie V., Ashby, Mark, Hellmann, Sue, Fyfe, Gwen, Vadhan‐Raj, Saroj, Champlin, Richard, Gajewski, James, Somlo, George
• Format: Journal Article
• Language: English
• Published: Bristol John Wiley & Sons, Ltd 01-05-1998
• Subjects: Adolescent; Adult; Aged; Blood Platelets - cytology; Blood Platelets - drug effects; Blood Platelets - metabolism; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Chemotherapy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - adverse effects; Humans; Middle Aged; Myeloablative; Myelosuppression; Platelet transfusion; Radiotherapy - adverse effects; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Thrombocytopenia - drug therapy; Thrombopoietin; Thrombopoietin - administration & dosage; Thrombopoietin - adverse effects
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.5530160723

Patients undergoing anticancer therapy are often at risk for developing severe and/or prolonged posttreatment thrombocytopenia. This can be associated with significant bleeding; currently, it is treated with supportive platelet transfusions. Frequent platelet transfusions can cause alloimmunization which requires HLA‐matched donors and more frequent blood transfusions, and transmission of both viral and bacterial infections via platelet transfusions remains a concern. Furthermore, thrombocytopenia can mandate a decrease in the dose intensity of cytotoxic therapy by causing either delays or dose reductions in therapy administration. An intervention that reduces the risk or shortens the duration of severe thrombocytopenia would represent an important medical advance.
Thrombopoietin (TPO), a naturally occurring, glycosylated polypeptide that was cloned by Genentech in 1994, is capable of inducing differentiation of stem cells into megakaryocytes and accelerating the maturation of megakaryocytes, thereby increasing the platelet count. Recombinant human TPO (rHuTPO) is currently undergoing testing in phase 1 and 2 studies in patients receiving myelosuppressive or myeloablative therapy. For the purposes of illustration, preliminary safety and activity data from one ongoing phase 1 myelosuppression trial (rHuTPO in women with advanced gynecologic malignancies receiving carboplatin) and one ongoing phase 1 myeloablation trial (rHuTPO for peripheral blood progenitor cell mobilization prior to myeloablative chemotherapy for high risk breast cancer) will be presented.