BMC Cancer (Mar 2021)

Randomized and dose-escalation trials of recombinant human serum albumin /granulocyte colony-stimulating factor in patients with breast cancer receiving anthracycline-containing chemotherapy

  • Shanshan Chen,
  • Yiqun Han,
  • Quchang Ouyang,
  • Jianguo Lu,
  • Qingyuan Zhang,
  • Shun’e Yang,
  • Jingfen Wang,
  • Haixin Huang,
  • Hong Liu,
  • Zhimin Shao,
  • Hui Li,
  • Zhendong Chen,
  • Sanyuan Sun,
  • Cuizhi Geng,
  • Junguo Lu,
  • Jianwei Sun,
  • Jiayu Wang,
  • Binghe Xu

DOI
https://doi.org/10.1186/s12885-021-08093-z
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 11

Abstract

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Abstract Background To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. Methods The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg. Results Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF. Conclusion The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. Trial registration ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).

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