des Guetz G, Mariani P, Cucherousset J, Benamoun M, Lagorce C, Sastre X, Le Toumelin P, Uzzan B, Perret G Y, Morere J F, Breau J L, Fagard R, Schischmanoff P O
Department of Oncology, Avicenne Hospital, 93009 Bobigny, France.
Anticancer Res. 2007 Jul-Aug;27(4C):2715-9.
Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer.
Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria.
Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients.
No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.
微卫星不稳定性（MSI）是错配修复基因失活的结果，约15%的结肠癌病例中可观察到。MSI结肠癌患者无法从基于5-氟尿嘧啶（5-FU）的化疗中获益。目前结肠癌的标准治疗方案是5-FU与奥沙利铂联合（FOLFOX）。本研究的目的是确定FOLFOX方案治疗转移性MSI结肠癌患者的疗效。
收集接受改良FOLFOX 4或FOLFOX 6治疗的转移性结肠癌患者的肿瘤标本；这两种方案分别基于85mg/m²和100mg/m²的奥沙利铂。通过测量五个单态单核苷酸标记的长度评估MSI状态。根据世界卫生组织标准，将FOLFOX方案作为一线治疗进行评估。
40例患者（22例男性，18例女性），中位年龄63.5岁（27 - 83岁）接受了FOLFOX 4或6治疗。9例患者的肿瘤表现为高度MSI（MSI组），31例患者的肿瘤表现为微卫星稳定（MSS组）。在MSS组中，观察到11例部分缓解（36%），而MSI组仅有2例（22%）（无显著差异）。MSI组中的2例缓解者接受了FOLFOX 6治疗。MSI和MSS患者的总生存期无显著差异。
两组患者的总缓解率或总生存期无显著差异。然而，这些结果表明MSI结肠癌患者对更高剂量的FOLFOX更敏感。
