Jones S E, Khandelwal P, McIntyre K, Mennel R, Orr D, Kirby R, Agura E, Duncan L, Hyman W, Roque T, Regan D, Schuster M, Dimitrov N, Garrison L, Lange M
Texas Oncology, PA, Physician Reliance Network, and Sammons Cancer Center of Baylor University Medical Center, Dallas, TX 75246, USA.
J Clin Oncol. 1999 Oct;17(10):3025-32. doi: 10.1200/JCO.1999.17.10.3025.
To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III breast cancer.
In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 microg/m(2) subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/microL.
PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P <.05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug.
PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.
测定PIXY321（粒细胞-巨噬细胞集落刺激因子/白细胞介素-3酿酒酵母融合蛋白）对II期和III期乳腺癌患者接受中等剂量氟尿嘧啶600mg/m²、多柔比星60mg/m²和环磷酰胺750mg/m²（FAC）化疗后中性粒细胞减少和血小板减少的发生率、持续时间及并发症的影响。
在这项多中心、随机、双盲、安慰剂对照试验中，71名女性患者在第1天接受4个为期21天的中等剂量FAC化疗短程静脉输注周期治疗，随后在第3至15天接受安慰剂或PIXY321（375μg/m²皮下注射，每日2次）治疗。当绝对中性粒细胞计数低于1000/μL时，所有患者均接受预防性口服环丙沙星治疗。
PIXY321显著降低了第1和第2周期3级和4级中性粒细胞减少的发生率和持续时间，以及第1至4周期3级中性粒细胞减少的持续时间。在第3和第4周期，PIXY321组3级血小板减少明显更常见（P<.05）。PIXY321组有2名患者需要输注血小板。仅在第1周期，PIXY321组发热和因静脉使用抗生素住院明显更常见。在第1至3周期，PIXY321组更多患者在第22天实现血液学恢复，且在所有周期中PIXY321组恢复时间明显更短。PIXY321组FAC剂量强度约高2%（P=无显著性差异）。PIXY321组总体发生率显著更高的任何强度的非血液学事件包括注射部位反应、发热、寒战、腹痛和关节痛。没有患者在研究期间或最后一剂研究药物后30天内死亡。
PIXY321降低了第1和第2周期FAC诱导的3级和4级中性粒细胞减少的发生率和持续时间，并显著缩短了所有周期的血液学恢复时间。然而，它在第3和第4周期产生了更多的全身毒性以及血小板减少。
