Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Canada.
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Breast Cancer Res Treat. 2024 Dec;208(3):523-533. doi: 10.1007/s10549-024-07443-2. Epub 2024 Jul 31.
While adjuvant bisphosphonate use in early breast cancer (EBC) is associated with improvements in breast cancer-specific outcomes, questions remain around optimal bisphosphonate type, dose and scheduling. We evaluated a single zoledronate infusion in a prospective randomised trial.
Postmenopausal patients with EBC were randomised to receive a single infusion of zoledronate (4 mg IV) or 6-monthly treatment for 3 years. Outcomes measured were; Quality of Life (QoL; EQ-5D-5L), bisphosphonate-related toxicities, including acute phase reactions (APRs), recurrence-free survival (RFS), bone metastasis-free survival (BMFS) and overall survival (OS).
211 patients were randomized to either a single infusion (n = 107) or six-monthly treatment (n = 104). After 3 years of follow up there were no significant differences between the arms for QoL and most toxicity endpoints. APRs following zoledronate occurred in 81% (171/211) of patients (77.6% in single infusion arm and 84.6% in the 6-monthly group). While the frequency of APRs decreased over 3 years in the 6-monthly arm, they still remain common. Of 34/104 (32.7%) patients who discontinued zoledronate early in the 6-monthly treatment group, the most common reason was APRs (16/34, 47%). At the 3 year follow up, there were no differences between arms for RFS, BMFS or OS.
A single infusion of zoledronate was associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation. Despite the common clinical impression that APRs decrease with time, this was not observed when patients were specifically questioned. While the study is not powered for non-inferiority, longer-term follow-up for confirmation of RFS and OS rates is ongoing.
尽管辅助双磷酸盐在早期乳腺癌（EBC）中的应用与改善乳腺癌特异性结局相关，但关于最佳双磷酸盐类型、剂量和方案仍存在疑问。我们在一项前瞻性随机试验中评估了唑来膦酸单次输注。
绝经后 EBC 患者被随机分配接受唑来膦酸（4mg IV）单次输注或 6 个月治疗 3 年。测量的结果是：生活质量（QoL；EQ-5D-5L）、双磷酸盐相关毒性，包括急性期反应（APR）、无复发生存率（RFS）、无骨转移生存（BMFS）和总生存（OS）。
211 例患者被随机分配至单次输注组（n=107）或 6 个月治疗组（n=104）。在 3 年的随访后，两组之间在 QoL 和大多数毒性终点方面均无显著差异。211 例患者中有 81%（171/211）出现了唑来膦酸 APR（单次输注组为 77.6%，6 个月组为 84.6%）。虽然在 6 个月组中 APR 的频率在 3 年内有所下降，但它们仍然很常见。在 6 个月治疗组中，有 34/104（32.7%）的患者早期停用了唑来膦酸，最常见的原因是 APR（16/34，47%）。在 3 年随访时，两组之间在 RFS、BMFS 或 OS 方面没有差异。
唑来膦酸单次输注与增加患者便利性、降低毒性和降低治疗中断率相关。尽管临床上普遍认为 APR 随时间减少，但当具体询问患者时，并未观察到这种情况。虽然该研究没有进行非劣效性检验，但正在进行更长时间的随访以确认 RFS 和 OS 率。
