美国弗吉尼亚州亚历山大市——初诊为转移性结直肠癌的患者III期试验数据的前瞻性分析表明，高浓度的维生素D的患者在化疗和靶向治疗后疗效较好。高浓度的维生素D的患者的总生存期的中位数为32.6个月，而低浓度的维生素D的患者的总生存期的中位数仅为24.5个月。该研究将在2015年1月15日-17日在旧金山举行的ASCO GI研讨会上公布。

该研究为临床前期和流行病学研究中观察到的维生素D的抗肿瘤疗效增加了新的证据。确认在癌症诊断前后补充维生素D的价值的随机试验正在进行当中。

研究详情

背景：前瞻性的流行病学数据提示，高浓度的维生素D[25(OH)D]能够延长结直肠癌患者的生存期。然而，目前还不清楚25(OH)D与转移性结直肠癌患者的预后之间的关系。

方法：我们打算评估参与CALGB 80405试验的初治的转移性结直肠癌患者血浆25(OH)D的浓度和总生存期之间的关系。该试验是一个III期的随机试验，评估了化疗+贝伐单抗、化疗+西妥昔单抗或化疗+西妥昔单抗+贝伐单抗在转移性结直肠癌患者中的疗效（在确定为KRAS野生型以前）。无进展生存期是次要评价指标。

通过放射免疫分析法测定血浆中25(OH)D的浓度，并通过自填问卷来收集患者的饮食和生活方式的信息。校正其他预后因素后，应用COX比例风险模型来计算风险比。在敏感度分析中，评估逆向因果关系的可能性时，要排除抽血3个月或6个月内死亡的患者。

结果：1043位患者中，血浆25(OH)D浓度的中位数为17.2 ng/mL (范围 2.2-72.7)。老年患者和黑人患者、进食少的患者和维生素D摄入量少的患者、ECOG体力状态评分为1的患者、体重指数高的患者、缺乏体育锻炼的患者和在冬天和春天抽血的患者25(OH)D的浓度明显较低。在对病理和临床预后因素进行校正后，5组中25(OH)D浓度最高的患者的总生存期明显长于25(OH)D浓度最低的患者(中位数分别为32.6 vs. 24.5个月; HR 0.67, 95% CI, 0.53-0.86; p=0.002)。增加25(OH)D的浓度也能明显延长无进展生存期(浓度最高的患者和浓度最低的患者的无进展生存期分别为12.2 vs. 10.1个月; HR 0.80, 95% CI, 0.64-1.01; p = 0.02)。结果与各亚组患者的特点相一致，包括KRAS突变状态。在排除抽血3个月或6个月内死亡的患者后，结果保持不变。

结论：高浓度的血浆25(OH)D能够明显延长应用化疗+生物制剂治疗的转移性结直肠癌患者的生存期。我们需要进行补充维生素D的随机试验，这样的试验目前已经在进行当中。

作者观点

我们的研究显示高浓度的维生素D也能明显延长生存期。我们的最终目标是通过补充维生素D来治疗结直肠癌的随机试验来将该研究转化为一种有效的治疗措施。该文章的主要作者——马萨诸塞州波士顿市哈佛大学Dana-Farber 癌症研究所的医学助理教授Kimmie Ng博士说道。现在推荐维生素D作为结直肠癌的治疗药物还太早，但是我们知道维持高浓度的维生素D对健康有其他的好处，例如骨的健康。

Ng医生指出，一个正在进行中的临床试验正在检测补充维生素D对癌症预防和治疗的影响。

ASCO 专家观点

除了能延长生存期外，高浓度的维生素D还能延缓癌症对化疗的抵抗出现的时间，这提示维生素D可以降低癌症的生长速度或增加治疗的活性。今日新闻的主持人、ASCO的专家Smitha S. Krishnamurthi博士说道。我们需要进一步的研究来确认生存期的延长是由维生素D本身造成的还是与高浓度的维生素D有关的其他因素造成的。

医脉通编译整理，转载请注明出处。

阅读英文摘要

Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). （Abstract 507）

Session：General Poster Session C

Authors: Kimmie Ng, Alan P. Venook, Kaori Sato, Bruce W. Hollis, Donna Niedzwiecki, Cynthia Ye, I-Wen Chang, Bert H. O'Neil, Federico Innocenti, Heinz-Josef Lenz, Charles David Blanke, Robert J. Mayer, Charles S. Fuchs, Jeffrey A. Meyerhardt; Dana-Farber Cancer Institute, Boston, MA; University of California, San Francisco, San Francisco, CA; Medical University of South Carolina, Charleston, SC; Alliance Statistics and Data Center, Durham, NC; Duke University, Durham , NC; Southeastern Medical Oncology, Goldsboro, NC; Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; The University of North Carolina at Chapel Hill, Chapel Hill, NC; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; SWOG and Oregon Health & Science University, Portland, OR 

Background: Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer (CRC), however, the relationship between 25(OH)D and outcome in metastatic CRC, specifically, is unknown. 

Methods: We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Progression-free survival (PFS) was a secondary endpoint. 

Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios adjusted for other prognostic factors. In sensitivity analyses, patients who died within 3 or 6 months of blood draw were excluded to address the possibility of reverse causation. 

Results: Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Older and black patients, those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.67, 95% CI, 0.53-0.86; p trend 0.002). Increasing concentrations of 25(OH)D were also associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.80, 95% CI, 0.64-1.01; p trend = 0.02). The results were consistent across subgroups of patient characteristics, including KRAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. 

Conclusions: Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and are currently underway.

查看会议专题》》》2015 ASCO胃肠肿瘤(GI)研讨会

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