[Phase I clinical trail of intravenous pegylated recombinant human granulocyte colony-stimulating factor].

Abstract

BACKGROUND & 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.

• Authors: Yuan-Kai Shi, Peng Liu, Sheng Yang, Xiao-Hong Han, Xiao-Hui He, Bin Ai, Yan Qin, Bo Li, Ding-Zhi Huang, Chang-Gong Zhang, Yan Sun
• Journal: Ai zheng = Aizheng = Chinese journal of cancer (Ai Zheng) Vol. 25 Issue 4 Pg. 495-500 (Apr 2006) China
• PMID: 16613688 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antigens, CD34
• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• Polyethylene Glycols
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Antigens, CD34 (metabolism)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Agents, Phytogenic (adverse effects, therapeutic use)
• Arthralgia (chemically induced)
• Blood Cell Count
• Breast Neoplasms (drug therapy)
• Carboplatin (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Fatigue (chemically induced)
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage, adverse effects, chemistry, therapeutic use)
• Humans
• Injections, Subcutaneous
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Neutropenia (chemically induced, drug therapy, pathology)
• Neutrophils (cytology)
• Paclitaxel (adverse effects, therapeutic use)
• Polyethylene Glycols (chemistry)
• Recombinant Proteins