Strippoli Antonia, Rossi Sabrina, Martini Maurizio, Basso Michele, D'Argento Ettore, Schinzari Giovanni, Barile Rosalba, Cassano Alessandra, Barone Carlo
Department of Medical Oncology, Catholic University of Sacred Heart, 00168 Rome, Italy.
Department of Pathology, Catholic University of Sacred Heart, 00168 Rome, Italy.
Oncotarget. 2016 Jun 7;7(23):35159-68. doi: 10.18632/oncotarget.9063.
No clinically useful predictive factor has been yet identified for treatment of metastatic pancreatic cancer (mPC). It is noteworthy that FOLFIRINOX, despite its high toxicity, is effective only in some patients. We retrospectively analyzed expression of excision repair cross-complementing group-1 (ERCC1) - involved in the repair of platinum induced damage - in patients affected by mPC treated with FOLFIRINOX in order to evaluate its predictive role.
FOLFIRINOX resulted more effective in patients with normal ERCC1 levels than in those with ERCC1 hyper-expression. Median progression free survival (PFS) was 11 vs. 4 months (HR 0.26; 95% CI 0.14-0.50; p<.0001), median overall survival (OS) 16 vs. 8 months (HR 0.23; 95% CI 0.12-0.46; p<.0001) and disease control rate (DCR) 93% vs. 50% (p=0.00006). The advantage was confirmed at univariate and multivariate analysis.
71 patients with histologically proven mPC and treated with FOLFIRINOX as first-line therapy were considered eligible. mRNA ERCC1 expression was determined using RT-PCR analysis.
ERCC1 might be an effective predictor of response to FOLFIRINOX in mPC. Patients overexpressing ERCC1 should be excluded by this often toxic therapy and referred to an alternative treatment.
目前尚未发现可用于转移性胰腺癌（mPC）治疗的具有临床实用价值的预测因素。值得注意的是，FOLFIRINOX方案尽管毒性高，但仅对部分患者有效。我们回顾性分析了参与铂诱导损伤修复的切除修复交叉互补组1（ERCC1）在接受FOLFIRINOX治疗的mPC患者中的表达情况，以评估其预测作用。
ERCC1水平正常的患者接受FOLFIRINOX治疗的效果优于ERCC1高表达的患者。中位无进展生存期（PFS）分别为11个月和4个月（风险比[HR] 0.26；95%置信区间[CI] 0.14 - 0.50；p <.0001），中位总生存期（OS）分别为16个月和8个月（HR 0.23；95% CI 0.12 - 0.46；p <.0001），疾病控制率（DCR）分别为93%和50%（p = 0.00006）。单因素和多因素分析均证实了这一优势。
71例经组织学证实为mPC且接受FOLFIRINOX作为一线治疗的患者被认为符合条件。采用逆转录聚合酶链反应（RT-PCR）分析测定ERCC1的mRNA表达。
ERCC1可能是mPC患者对FOLFIRINOX治疗反应的有效预测指标。ERCC1过表达的患者应排除在这种常有毒性的治疗方案之外，并转至其他治疗方案。
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