Jie Xie1,2, Jun Cao1,2, Jing-Fen Wang3, Bai-Hong Zhang4, Xiao-Hua Zeng5, Hong Zheng5, Yang Zhang6, Li Cai7, Yu-Dong Wu8, Qiang Yao9, Xiao-Chun Zhao10, Wei-Dong Mao11, Ai-Mei Jiang12, Shao-Shui Chen13, Shun-E Yang14, Shu-Sen Wang15, Jian-Hong Wang16, Yue-Yin Pan17, Bi-Yong Ren18, Yan-Ju Chen19, Li-Zhi Ouyang20, Kai-Jian Lei21, Jing-Hua Gao22, Wen-He Huang23, Zhan Huang24, Tao Shou25, Yan-Ling He26, Jing Cheng27, Yang Sun28, Wei-Ming Li29, Shu-de Cui30, Xin Wang31, Zhi-Guo Rao32, Hu Ma33, Wei Liu34, Xue-Yong Wu35, Wei-Xi Shen36, Fei-Lin Cao37, Ze-Min Xiao38, Biao Wu39, Shu-Yan Tian40, Dong Meng41, Peng Shen42, Bi-Yun Wang1,2, Zhonghua Wang1,2, Jian Zhang1,2, Leiping Wang1,2, Xi-Chun Hu43,44. 1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China. 3. Linyi Tumor Hospital, Linyi, 276001, China. 4. Lanzhou Military General Hospital of People's Liberation Army, Gansu Lanzhou, 730050, China. 5. Chongqing Cancer Hospital, Chongqing, 400030, China. 6. Liaocheng People's Hospital, Liaocheng, 252000, China. 7. The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China. 8. Jiangxi Cancer Hospital, Nanchang, 330029, China. 9. Tianjin People's Hospital, Tianjin, 300121, China. 10. The First Affiliated Hospital Of University Of South China, Hengyang, 421001, China. 11. The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, 214400, China. 12. First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China. 13. Binzhou Medical School Affiliated Hospital, Binzhou, 256603, China. 14. Tumour Hospital Affiliated To Xinjiang Medical University, Urumqi, 830000, China. 15. Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. 16. Nantong Tumor Hospital, Nantong, 226361, China. 17. The First Affiliated Hospital Of Anhui Medical University, Hefei, 230022, China. 18. Chongqing Three Gorges Central Hospital, Chongqing, 404000, China. 19. Hainan General Hospital, Haikou, 570311, China. 20. Hunan Cancer Hospital, Changsha, 410006, China. 21. The Second People's Hospital of Yibin, Yibin, 644000, China. 22. Cangzhou Central Hospital, Cangzhou, 061001, China. 23. Cancer Hospital of Shantou University Medical College, Shantou, 515000, China. 24. Yue Bei People's Hospital, Shaoguan, 512025, China. 25. The First People's Hospital of Yunnan Province, Kunming, 650032, China. 26. Peking University Shenzhen Hospital, Shenzhen, 518036, China. 27. Huazhong University of Science and Technology Wuhan Union Hospital, Wuhan, 430022, China. 28. People's Hospital of Sanya, Sanya, 572000, China. 29. The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. 30. Henan Cancer Hospital, Zhengzhou, 450008, China. 31. Zhongshan Hospital Affiliated To Xiamen University, Xiamen, 361004, China. 32. Wuhan General Hospital of Guangzhou Military, Wuhan, 430070, China. 33. Affiliated Hospital of Zunyi Medical College, Zunyi, 563000, China. 34. Affiliated Hospital of Beihua University, Jilin, 132011, China. 35. Jing'an District Centre Hospital of Shanghai, Shanghai, 200040, China. 36. Shenzhen People's Hospital, Shenzhen, 518020, China. 37. Taizhou Hospital of Zhejiang Province, Taizhou, 317000, China. 38. The First People's Hospital of Changde City, Changde, 415003, China. 39. The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. 40. The Centre Hospital of Siping City, Siping, 136000, China. 41. Wu Xi No.4 People's Hospital, Wuxi, 214000, China. 42. The First Affiliated Hospital Of Zhejiang University, Hangzhou, 310003, China. 43. Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. xchu_fuscc@163.com. 44. Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China. xchu_fuscc@163.com.
Abstract
BACKGROUND:PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS:PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.
RCT Entities:
BACKGROUND:PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancerpatients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS:PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancerpatients receiving multiple cycles of chemotherapy.
Entities:
Keywords:
Breast cancer; Multicenter study; Neutropenia; PEG-rhG-CSF