Clinical studies of 2 forms of recombinant thrombopoietin in chemotherapy-induced thrombocytopenia
| Form . | Investigator . | Disease . | No. of patients . | Chemotherapy . | Dose (μg/kg) . | Route . | Prechemotherapy phase . | Postchemotherapy phase . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Dosing . | Outcome . | Dosing . | Outcome . | |||||||
| PEG-rHuMGDF | Fanucchi et al98 | Non-small-cell lung cancer | PEG-rHuMGDF = 41 | Carboplatin, paclitaxel | 0.03-5.0 | SC | Daily up to 10 d | Increase in platelets in 2 of 3 patients treated* | Daily up to 16 d | Increased recovery of platelets to baseline level |
| Placebo = 12 | Nadir platelet counts increased | |||||||||
| Basser et al99 105 | Advanced cancer | PEG-rHuMGDF = 31 | Carboplatin, cyclophosphamide | 0.03-5.0 | SC | Daily up to 10 d | Dose-related increase in platelets† 0.03-0.1 μg/kg per day | Daily for 7 to 20 d | Increased recovery of platelets to baseline level | |
| Placebo = 10 | → no increase in platelets 0.3-1.0 μg/kg per day | Platelet nadir earlier but nadir platelet count unaffected | ||||||||
| → median 3-fold increase in platelets | ||||||||||
| Crawford et al100 | Non-small-cell lung cancer | PEG-rHuMGDF = 30 | Carboplatin, paclitaxel | 2.5-5.0 | SC | NA | NA | Daily up to 7 d | Dose-related increase in platelet nadir | |
| Placebo = 10 | Reduction in number of platelet transfusions required in first 2 cycles | |||||||||
| Dose-limiting thrombocytopenia in later cycles | ||||||||||
| Anti-TPO antibodies in 2 patients | ||||||||||
| Basser et al106 | Advanced cancer | PEG-rHuMGDF = 68 | Carboplatin, cisplatin | 1.0-10.0 | SC | NA | NA | Multiple daily doses up to 7 d | Increased platelet nadir (47.5 × 109/L versus 35.5×109/L; P =.003) and decreased duration of grade 3 or 4 thrombocytopenia (0 versus 3 days; P =.004) with PEG-rHuMGDF | |
| rhTPO | Vadhan-Raj et al101 102 | Sarcoma | rhTPO = 12 | Doxorubicin, ifosfamide | 0.3-2.4 | IV | Single | Dose-related 1.3-3.6-fold increase in platelets | 1, 2, 3, or 7 daily doses | Decreased (schedule-dependent) thrombocytopenia Increased platelet recovery |
| Vadhan-Raj et al103 104 | Gynecologic malignancy | rhTPO = 29 | Carboplatin | 0.6-3.6 | SC | Single | Dose-related 1.1-3.5-fold increase in platelets | 4 daily doses | Decrease in both degree and duration of severe thrombocytopenia and the need for platelet transfusions | |
| Form . | Investigator . | Disease . | No. of patients . | Chemotherapy . | Dose (μg/kg) . | Route . | Prechemotherapy phase . | Postchemotherapy phase . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Dosing . | Outcome . | Dosing . | Outcome . | |||||||
| PEG-rHuMGDF | Fanucchi et al98 | Non-small-cell lung cancer | PEG-rHuMGDF = 41 | Carboplatin, paclitaxel | 0.03-5.0 | SC | Daily up to 10 d | Increase in platelets in 2 of 3 patients treated* | Daily up to 16 d | Increased recovery of platelets to baseline level |
| Placebo = 12 | Nadir platelet counts increased | |||||||||
| Basser et al99 105 | Advanced cancer | PEG-rHuMGDF = 31 | Carboplatin, cyclophosphamide | 0.03-5.0 | SC | Daily up to 10 d | Dose-related increase in platelets† 0.03-0.1 μg/kg per day | Daily for 7 to 20 d | Increased recovery of platelets to baseline level | |
| Placebo = 10 | → no increase in platelets 0.3-1.0 μg/kg per day | Platelet nadir earlier but nadir platelet count unaffected | ||||||||
| → median 3-fold increase in platelets | ||||||||||
| Crawford et al100 | Non-small-cell lung cancer | PEG-rHuMGDF = 30 | Carboplatin, paclitaxel | 2.5-5.0 | SC | NA | NA | Daily up to 7 d | Dose-related increase in platelet nadir | |
| Placebo = 10 | Reduction in number of platelet transfusions required in first 2 cycles | |||||||||
| Dose-limiting thrombocytopenia in later cycles | ||||||||||
| Anti-TPO antibodies in 2 patients | ||||||||||
| Basser et al106 | Advanced cancer | PEG-rHuMGDF = 68 | Carboplatin, cisplatin | 1.0-10.0 | SC | NA | NA | Multiple daily doses up to 7 d | Increased platelet nadir (47.5 × 109/L versus 35.5×109/L; P =.003) and decreased duration of grade 3 or 4 thrombocytopenia (0 versus 3 days; P =.004) with PEG-rHuMGDF | |
| rhTPO | Vadhan-Raj et al101 102 | Sarcoma | rhTPO = 12 | Doxorubicin, ifosfamide | 0.3-2.4 | IV | Single | Dose-related 1.3-3.6-fold increase in platelets | 1, 2, 3, or 7 daily doses | Decreased (schedule-dependent) thrombocytopenia Increased platelet recovery |
| Vadhan-Raj et al103 104 | Gynecologic malignancy | rhTPO = 29 | Carboplatin | 0.6-3.6 | SC | Single | Dose-related 1.1-3.5-fold increase in platelets | 4 daily doses | Decrease in both degree and duration of severe thrombocytopenia and the need for platelet transfusions | |
NA indicates not applicable; PEG-rHuMGDF, pegylated recombinant human megakaryocyte growth and development factor; rhTPO, recombinant human thrombopoietin; SC subcutaneous; and IV, intravenous.
Six patients (3 placebo, 3 PEG-rHuMGDF) were evaluated in the prechemotherapy phase.
Seventeen patients (4placebo, 13 PEG-rHuMGDF) were evaluated in the prechemotherapy phase.