[Phase I clinical trail of intravenous pegylated recombinant human granulocyte colony-stimulating factor].
OBJECTIVE
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in the prophylaxis and management of chemotherapy-induced neutropenia, but requires daily administration because of its short half-life. Pegylated rhG-CSF (PEG-rhG-CSF) is a long-acting reagent that permits less frequent injection. This study was to evaluate the safety and tolerance of PEG-rhG-CSF in Chinese patients, and to explore its efficacy of enhancing absolute neutrophil count (ANC) and CD34+ cell count in peripheral blood.


METHODS
Naïve non-small lung cancer or breast cancer patients with normal bone marrow function were eligible for this open-labeled, dose-escalation trial. All patients received 2 cycles of chemotherapy of identical regimen. In cycle 1, rhG-CSF (150 microg/day) was administrated in case of febrile neutropenia or grade 4 neutropenia; in cycle 2, patients received a single injection of PEG-rhG-CSF (30 microg/kg, 60 microg/kg, 100 microg/kg, or 200 microg/kg) 48 h after administration of paclitaxel and carboplatin.


RESULTS
All the 16 patients enrolled (4 in each dose group) were evaluable for safety and efficacy of PEG-rhG-CSF. Main adverse events related to PEG-rhG-CSF were musculoskeletal pain or arthralgia (13/16), fatigue (10/16), dizziness (2/16), and injection-site pain (1/16). All adverse events were mild to moderate, and most of them were reversible without treatment. PEG-rhG-CSF enhanced ANC in a dose-dependent manner to some extent, and PEG-rhG-CSF at 60 microg/kg or higher doses prevented chemotherapy-induced neutropenia with sustained effect; CD34+ cells in peripheral blood were also increased.


CONCLUSIONS
PEG-rhG-CSF is well tolerated, with no serious adverse event in this trial. The recommended dose of PEG-rhG-CSF for phase II trial is 100 microg/kg because of its adequate efficacy and less adverse events than those of 200 microg/kg.
Shi
Yuan-Kai
YK
Department of Medical Oncology, Cancer Hospital/Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P. R. China. syk@pubem.cicams.ac.cn
Liu
Peng
P
Yang
Sheng
S
Han
Xiao-Hong
XH
He
Xiao-Hui
XH
Ai
Bin
B
Qin
Yan
Y
Li
Bo
B
Huang
Ding-Zhi
DZ
Zhang
Chang-Gong
CG
Sun
Yan
Y
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D018771:Arthralgia / Q000139:chemically induced; D001772:Blood Cell Count; D001943:Breast Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009504:Neutrophils / Q000166:cytology; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D016190:Carboplatin; D017239:Paclitaxel