Recombinant human thrombopoietin clinical development.
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.
Jones
D V
DV
Genentech, Inc., South San Francisco, California, USA.
Ashby
M
M
Vadhan-Raj
S
S
Somlo
G
G
Champlin
R
R
Gajewski
J
J
Hellmann
S
S
Fyfe
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000188:drug therapy*; D013926:Thrombopoietin / Q000008:administration & dosage* / Q000009:adverse effects
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin