Comparing Trial and Real-world Adjuvant Oxaliplatin Delivery in Patients With Stage III Colon Cancer Using a Longitudinal Cumulative Dose.

IF 22.5 1区 医学 Q1 ONCOLOGY
Michael Webster-Clark, Alexander P Keil, Nicholas Robert, Jennifer R Frytak, Marley Boyd, Til Stürmer, Hanna Sanoff, Daniel Westreich, Jennifer L Lund
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引用次数: 0

Abstract

Importance: Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received.

Objective: To compare oxaliplatin delivery between MOSAIC trial participants and patients treated in the US Oncology Network with stage III colon cancer using a longitudinal cumulative dose (LCD).

Design, setting, and participants: This cohort study used secondary data from the MOSAIC trial, an international randomized clinical trial (concluded in 2004), and electronic health records from US Oncology (2009-2018), a network of community oncology practices in the US. It included participants in MOSAIC with stage III colon cancer who were randomized to receive treatment with oxaliplatin and fluorouracil/leucovorin (n = 663) and US Oncology patients with stage III colon cancer who were treated with a modified FOLFOX-6 regimen (n = 2523).

Exposures: Oxaliplatin and fluorouracil/leucovorin.

Outcomes and measures: We evaluated RDI and LCD over time and at the end of treatment in the MOSAIC and US Oncology populations. We used bootstrapping to estimate 95% confidence bands for LCD differences between the populations.

Results: The 663 MOSAIC participants (296 women [44.7%]) and 2523 US Oncology patients (1245 women [49.4%]) were generally similar with respect to demographic characteristics. Median RDI was lower in US Oncology (80% in MOSAIC vs 70% in US Oncology). The LCD also suggested differences in the total amount of oxaliplatin received between populations; the final median LCD in US Oncology was 10.2% lower than in MOSAIC, equivalent to receiving 1.2 fewer treatment cycles less of oxaliplatin. This difference only began 133 days into treatment and persisted after accounting for covariates, likely in terms of more frequent oxaliplatin treatment discontinuation in US Oncology patients than their MOSAIC counterparts.

Conclusions and relevance: The study results suggest that real-world patients in community practice in the US treated with modified FOLFOX 6 received less oxaliplatin than their historical counterparts in the MOSAIC trial, with differences manifesting late in the treatment course. The LCD allowed us to identify the amount and extent of these differences, the timing of which was unclear when using RDI alone.

Trial registration: ClinicalTrials.gov identifier: NCT00275210.

使用纵向累积剂量比较试验和现实世界辅助奥沙利铂在癌症III期患者中的递送。
重要性:辅助化疗的交付可能在试验和现实世界的人群之间有很大差异。相对剂量强度(RDI)等依从性指标无法捕捉修改的时间和所接受化疗总量的差异。目的:使用纵向累积剂量(LCD)比较MOSAIC试验参与者和在美国肿瘤网络接受治疗的癌症III期结肠癌患者之间的奥沙利铂给药。设计、设置和参与者:这项队列研究使用了MOSAIC试验的二级数据,这是一项国际随机临床试验(于2004年结束),以及美国肿瘤学(2009-2018年)的电子健康记录,美国肿瘤学是一个美国社区肿瘤学实践网络。它包括了患有III期结肠癌癌症的MOSAIC参与者,他们被随机分配接受奥沙利铂和氟尿嘧啶/亚叶酸治疗(n = 663)和用改良FOLFOX-6方案治疗的患有III期结肠癌癌症的美国肿瘤患者(n = 2523)。暴露:奥沙利铂和氟尿嘧啶/亚叶酸。结果和测量:我们评估了MOSAIC和美国肿瘤学人群随时间和治疗结束时的RDI和LCD。我们使用自举来估计群体之间LCD差异的95%置信区间。结果:663名MOSAIC参与者(296名女性[44.7%])和2523名美国肿瘤患者(1245名女性[49.4%])在人口统计学特征方面总体相似。美国肿瘤学的中位RDI较低(MOSAIC为80%,美国肿瘤学为70%)。LCD还表明,不同人群接受的奥沙利铂总量存在差异;美国肿瘤学的最终中位LCD比MOSAIC低10.2%,相当于接受的奥沙利铂治疗周期减少了1.2个。这种差异仅在治疗133天后开始,并在考虑协变量后持续存在,可能是因为美国肿瘤患者比MOSAIC患者更频繁地停止奥沙利铂治疗。结论和相关性:研究结果表明,在美国社区实践中,接受改良FOLFOX 6治疗的真实世界患者比MOSAIC试验中的历史患者接受的奥沙利铂更少,差异在治疗过程后期表现出来。LCD使我们能够识别这些差异的数量和程度,单独使用RDI时,差异的时间尚不清楚。试验注册:ClinicalTrials.gov标识符:NCT00275210。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JAMA Oncology
JAMA Oncology Medicine-Oncology
自引率
1.80%
发文量
423
期刊介绍: JAMA Oncology is an international peer-reviewed journal that serves as the leading publication for scientists, clinicians, and trainees working in the field of oncology. It is part of the JAMA Network, a collection of peer-reviewed medical and specialty publications.
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