转移性结肠癌的化疗：由于副作用而减少剂量时，对生存没有影响。
Chemotherapy for metastatic colon cancer: No effect on survival when the dose is reduced due to side effects.
机构信息
Department of Internal Medicine I, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 95053, Regensburg, Germany.
Cancer Center, Institute for quality assurance and health services research, University of Regensburg, Regensburg, Germany.
出版信息
BMC Cancer. 2018 Apr 23;18(1):455. doi: 10.1186/s12885-018-4380-z.
BACKGROUND
5-Fluorouracil (5FU), Folinic acid (FA), and Oxaliplatin (FOLFOX) or 5FU, FA, and Irinotecan (FOLFIRI) are standard regimens for palliative chemotherapy of metastatic colon cancer. Since data showing the influence of dose reduction in palliative treatment are rare, the objective of this single center, retrospective study was to further characterize the influence of dose reduction on efficacy of these therapeutic regimens.
METHODS
One hundred nine patients, diagnosed with stage IV colon cancer between 2004 and 2012 and receiving palliative first-line chemotherapy with either FOLFOX or FOLFIRI regimens in our outpatient clinic were analyzed for treatment efficacy. Patients who received dose reductions due to side effects usually received doses of 80% or lower of per protocol dose. Survival data were obtained from the Regensburg Tumor Registry. Survival analysis was performed using Kaplan-Meier statistical analysis and multivariable analysis.
RESULTS
A dose reduction due to side effects was necessary in 46 (42%) patients. Dose reduction was independent of age. Major reasons for dose reduction were neutropenia (30%) followed by polyneuropathy (16%) and diarrhea (14%). Dosage was more often reduced in patients receiving FOLFOX based therapy. Comparison of patients with dose reduction versus patients with full dosage showed no significant difference on overall survival (p = 0.430). Subgroup analysis revealed dose reduction in patients with N2 stage disease was associated with improved survival. Patients who underwent dose reduction received more cycles of chemotherapy (13.7 vs. 10.8 cycles) and cumulative dosage was similar in both groups.
CONCLUSION
Contrary to our expectations, the need to reduce chemotherapy dosage due to side effects does not indicate a worse prognosis in our retrospective analysis. We believe this can in part be explained by better adaption to interindividual pharmacokinetics and longer time of treatment.
背景
5-氟尿嘧啶（5FU）、亚叶酸钙（FA）和奥沙利铂（FOLFOX）或 5FU、FA 和伊立替康（FOLFIRI）是转移性结直肠癌姑息化疗的标准方案。由于姑息治疗中剂量减少的数据很少，因此本单中心回顾性研究的目的是进一步描述这些治疗方案中剂量减少对疗效的影响。
方法
分析了 2004 年至 2012 年间在我们的门诊接受 FOLFOX 或 FOLFIRI 方案一线姑息化疗的 109 例诊断为 IV 期结肠癌患者的治疗效果。由于副作用而需要减少剂量的患者通常接受的剂量为方案剂量的 80%或以下。生存数据来自雷根斯堡肿瘤登记处。使用 Kaplan-Meier 统计分析和多变量分析进行生存分析。
结果
由于副作用需要减少剂量的患者有 46 例（42%）。剂量减少与年龄无关。减少剂量的主要原因是中性粒细胞减少症（30%），其次是多发性神经病（16%）和腹泻（14%）。接受 FOLFOX 为基础治疗的患者更常减少剂量。与全剂量组相比，剂量减少组的总生存期无显著差异（p=0.430）。亚组分析显示，N2 期疾病患者的剂量减少与生存改善相关。接受剂量减少的患者接受了更多周期的化疗（13.7 次 vs. 10.8 次），两组的累积剂量相似。
结论
与我们的预期相反，在我们的回顾性分析中，由于副作用需要减少化疗剂量并不表明预后更差。我们认为，这在一定程度上可以解释为更好地适应个体药代动力学和更长的治疗时间。
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