[Treatment of chemotherapy-induced neutropenia pegylated recombinant human granulocyte colony-stimulating factor: a multi-center randomized controlled phase II clinical study].
OBJECTIVE
To compare the efficacy and safety of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), and a single subcutaneous injection of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), a sustained-duration rhG-CSF, in chemotherapy-induced neutropenia.


METHODS
In the present randomized, open-label, match and cross-over study, enrolled 104 patients with previously untreated non-small cell lung cancer (NSCLC), breast cancer or non-Hodgkin's lymphoma and with normal bone marrow function from 13 centers were randomly divided into 2 matched groups, AB and BA group. Each patient received two cycles of chemotherapy of identical regimen. In the study cycle, the patients received a single subcutaneous injection of PEG-rhG-CSF 100 microg/kg on day 3; and in control cycle, daily subcutaneous infection of rhG-CSF 5 microg x kg(-1) x d(-1) began on day 3 and continued for 14 days or until the absolute neutrophil count (ANC) became > or = 5.0 x 10(9)/L twice after it decreased to the nadir. Efficacy and safety parameters were monitored.


RESULTS
The incidence rates of ANC < 1.5 x 10(9)/L in the 103 evaluable study cycles and 100 evaluable control cycles were 30.00% and 20.00% with the duration of 2.39 days and 2.35 days respectively. The incidence rates of grade 3 neutropenia were 7.77% and 7.00%; and that of grade 4 neutropenia were 5.80% and 4.00% respectively in the trial and control cycles. However, all the difference mentioned above did not reached statistical significance. None of the patients experienced febrile neutropenia. The ANC nadir was (7.55 +/- 5.25) x 10(9)/L and (8.42 +/- 5.57) x 10(9)/L (P = 0.257) respectively after receiving PEG-rhG-CSF and rhG-CSF. Compared with that of rhG-CSF group, the ANC profile of PEG-rhG-CSF group exhibited limited "overshoot" of neutrophils after the nadir. Subgroup analysis according to disease type yielded similar results. The safety profiles of the PEG-rhG-CSF and rhG-CSF groups were similar. Musculoskeletal pain or arthralgia occurred in 16.5% of the study cycles and 26.00% of the control cycles (P = 0.963), mostly mild or moderate. Other adverse effects such as fever, fatigue, dizziness, gastrointestinal effects and injection-site pain, were transient and easily manageable.


CONCLUSIONS
A single subcutaneous injection of PEG-rhG-CSF 100 microg/kg provides neutrophil support and a safety profile comparable to regimen of daily subcutaneous injection of rhG-CSF 5 microg x kg(-1) x d(-1) in Chinese patients receiving a variety of myelosuppressive chemotherapy regimens.
Shi
Yuan-kai
YK
Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
He
Xiao-hui
XH
Yang
Sheng
S
Wang
Hua-qing
HQ
Jiang
Ze-fei
ZF
Zhu
Yun-zhong
YZ
Ke
Xiao-yan
XY
Zhang
Yang
Y
Liu
Yun-peng
YP
Zhang
Wei-jing
WJ
Wang
Zhao
Z
Shi
Qing-zhi
QZ
Xie
Xiao-dong
XD
Zhang
He-long
HL
Wang
Jie-jun
JJ
Luo
De-yun
DY
Zheng
Qing-shan
QS
Sun
Rui-yuan
RY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018592:Cross-Over Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011092:Polyethylene Glycols / Q000737:chemistry; D011446:Prospective Studies; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols