Awan Arif, Ng Terry, Conter Henry, Raskin William, Stober Carol, Simos Demetrios, Pond Greg, Dhesy-Thind Sukhbinder, Mates Mihaela, Kumar Vikaash, Fergusson Dean, Hutton Brian, Saunders Deanna, Vandermeer Lisa, Clemons Mark
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada.
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
J Bone Oncol. 2020 Dec 13;26:100343. doi: 10.1016/j.jbo.2020.100343. eCollection 2021 Feb.
Adjuvant zoledronate is widely used in patients with early stage breast cancer (EBC), but its optimal duration and dosing interval is still unknown. While a single-dose of zoledronate can improve bone density for many years, a proper evaluation of its effects on breast cancer-related outcomes would require a large trial. In this pilot study we evaluated the feasibility of performing such a trial.
Eligible patients with EBC were randomised to receive either one dose of zoledronate or 7 doses (6-monthly dosing for 3 years). Feasibility was assessed by a combination of primary outcomes including: activation of at least 6 Ontario sites within a year, active participation (i.e. approaching eligible patients for study participation) of at least half of the medical oncologists, and enrolment of at least 100 patients across all sites within 9 months of the sixth site being activated.
All 6 sites were activated within 1 year and of 47 medical oncologists, 27 (57%) approached patients. Between November 2018 and April 2020, 211 eligible patients were randomised, 106 (50.2%) to a single dose of zoledronate and 105 (49.8%) to 6-monthly dosing. Baseline characteristics of randomised patients included; median age 59 (range 36-88), ER and/or PR positive (85%), Her2 positive (23%), menopausal status (premenopausal [19%], perimenopausal [6.7%] and postmenopausal [74%]) and 74% received neo/adjuvant chemotherapy.
All study feasibility endpoints were met in this trial comparing alternative schedules for adjuvant zoledronate. We will now seek funding for performing a larger efficacy trial.Trial registration: NCT03664687.
辅助性唑来膦酸广泛应用于早期乳腺癌（EBC）患者，但最佳疗程和给药间隔仍不明确。虽然单剂量唑来膦酸可在多年内改善骨密度，但要正确评估其对乳腺癌相关结局的影响需要进行大规模试验。在这项初步研究中，我们评估了开展此类试验的可行性。
符合条件的EBC患者被随机分配接受一剂唑来膦酸或7剂（每6个月给药一次，共3年）。通过以下主要结局指标综合评估可行性：一年内至少激活6个安大略省的研究点、至少一半的肿瘤内科医生积极参与（即接触符合条件的患者以参与研究）以及在第六个研究点激活后的9个月内所有研究点至少招募100名患者。
所有6个研究点均在1年内激活，47名肿瘤内科医生中有27名（57%）接触了患者。在2018年11月至2020年4月期间，211名符合条件的患者被随机分组，106名（50.2%）接受单剂量唑来膦酸，105名（49.8%）接受每6个月给药一次。随机分组患者的基线特征包括：中位年龄59岁（范围36 - 88岁），雌激素受体（ER）和/或孕激素受体（PR）阳性（85%），人表皮生长因子受体2（Her2）阳性（23%），绝经状态（绝经前[19%]、围绝经期[6.7%]和绝经后[74%]），74%接受新辅助/辅助化疗。
在这项比较辅助性唑来膦酸不同给药方案的试验中，所有研究可行性终点均已达成。我们现在将寻求资金以开展更大规模的疗效试验。试验注册号：NCT03664687。
