Zielinski Christoph, Lang Istvan, Beslija Semir, Kahan Zsuzsanna, Inbar Moshe J, Stemmer Salomon M, Anghel Rodica, Vrbanec Damir, Messinger Diethelm, Brodowicz Thomas
Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University Vienna - General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Central European Cooperative Oncology Group (CECOG), Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Br J Cancer. 2016 Jan 19;114(2):163-70. doi: 10.1038/bjc.2015.419. Epub 2015 Dec 10.
Correlations between development of hand-foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial.
Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV-CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV-CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed.
Among 277 patients treated with BEV-CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively.
This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV-CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.
文献报道了接受含卡培他滨（CAP）治疗的患者中手足综合征（HFS）的发生与疗效之间的相关性。我们在图兰朵（TURANDOT）随机III期试验中探讨了接受CAP加贝伐单抗（BEV）治疗的患者中HFS与疗效之间的关系。
既往未接受过针对局部复发/转移性乳腺癌（LR/mBC）化疗的HER2阴性LR/mBC患者被随机分为接受BEV加紫杉醇或BEV-CAP治疗，直至疾病进展或出现不可接受的毒性。该分析纳入了随机接受BEV-CAP且接受≥1剂CAP的患者。使用Cox比例风险分析，将HFS作为时间依赖性协变量（以避免高估HFS对疗效的影响），探讨HFS与总生存期（OS；主要终点）和无进展生存期（PFS；次要终点）之间的潜在关联。还进行了标志性分析。
在277例接受BEV-CAP治疗的患者中，154例（56%）发生了HFS。在多变量分析中，HFS发生后疾病进展或死亡风险降低了44%；死亡风险降低了56%。对OS的影响程度随着HFS分级的增加而增加。在最初3个月内发生HFS的患者中，从3个月标志性时间点开始计算的中位PFS为10.0个月，而未发生HFS的患者为6.2个月。两年OS率分别为63%和44%。
这项探索性分析表明，HFS的发生是接受BEV-CAP治疗的LR/mBC患者PFS和OS延长的有力预测指标。HFS的早期出现可能有助于促使患者继续治疗。
