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(Drug information on doxorubicin) (Adriamycin)/ifosfamide (Ifex) and one in gynecologic malignancies being treated with a carboplatin(Drug information on 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.