HOUSTONThrombopoietin-like drugs may be a better bet for
moderating the effects of chemotherapy-induced myelosuppression than
either granulocyte colony stimulating factor (G-CSF) or
granulocyte-macrophage colony stimulating factor (GM-CSF). Ongoing
clinical trials with a recombinant human thrombopoietin (rhTPO) were
described by Saroj Vadhan-Raj, MD, of Texas M. D. Anderson Cancer
Center in Houston, at a clinical investigators workshop. That
workshop was sponsored by M.D. Anderson and Pharmacia Oncology.
Stem cells give rise to megakaryocytes, which eventually
produce platelets. Other growth factors stimulate parts of this
process, but TPO mediates all stages of it, Dr. Vadhan-Raj
explained. The new rhTPO is being tested in three trials at M. D.
Anderson, two in sarcomas being treated with doxorubicin
(Adriamycin)/ifosfamide (Ifex) and one in gynecologic malignancies
being treated with a carboplatin (Paraplatin)-based regimen.
Platelet Counts Rise
Dr. Vadhan-Raj said that in phase I studies, a single dose, even at
the lowest level of 0.3 µg/kg, produced a significant rise in
platelet counts in patients treated with doxorubicin/ifosfamide. In a
separate study, a single 2.4 µg/kg dose in chemotherapy
naïve patients increased platelet counts by 250%. This
also raised the possibility of harvesting platelets for autologous
use in subsequent auto-transplantation, Dr. Vadhan-Raj said.
Treatment also reduced the need for platelet transfusions.
Researchers have been trying to determine the best time to administer
rhTPO. Optimal dosing may depend on the length of the chemotherapy
regimen and on when the platelet nadir occurs. Ongoing phase III
studies are examining these questions.