Chibaudel Benoist, Maindrault-Goebel Frédérique, Lledo Gérard, Mineur Laurent, André Thierry, Bennamoun Mostepha, Mabro May, Artru Pascal, Carola Elisabeth, Flesch Michel, Dupuis Olivier, Colin Philippe, Larsen Annette K, Afchain Pauline, Tournigand Christophe, Louvet Christophe, de Gramont Aimery
Hôpital Saint-Antoine, Paris Cedex 12, France.
J Clin Oncol. 2009 Dec 1;27(34):5727-33. doi: 10.1200/JCO.2009.23.4344. Epub 2009 Sep 28.
This study compared chemotherapy discontinuation with maintenance therapy with leucovorin and fluorouracil after six cycles of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy in the first-line treatment of metastatic colorectal cancer.
Two hundred two patients with untreated metastatic colorectal cancer were randomly assigned to receive six cycles of modified FOLFOX7 (mFOLFOX7) followed by simplified leucovorin plus bolus and infusional fluorouracil until progression (arm 1 or maintenance arm, n = 98) or six cycles of mFOLFOX7 before a complete stop of chemotherapy (arm 2 or chemotherapy-free interval [CFI] arm, n = 104). Reintroduction of mFOLFOX7 was scheduled after tumor progression in both arms. The primary study end point was duration of disease control (DDC).
Median DDC was 13.1 months in patients assigned to the maintenance arm and 9.2 months in patients assigned to the CFI arm (P = .046). Median progression-free survival (PFS) and overall survival were 8.6 and 23.8 months, respectively, in the maintenance arm and 6.6 and 19.5 months, respectively, in the CFI arm. Median duration of maintenance therapy (arm 1) and CFIs (arm 2) were 4.8 months and 3.9 months, respectively. Overall response rates were 59.2% and 59.6% for the initial FOLFOX chemotherapy and 20.4% and 30.3% for FOLFOX reintroduction in arms 1 and 2, respectively.
The planned complete discontinuation of chemotherapy had a negative impact on DDC and PFS compared with the maintenance therapy strategy. These results suggest that chemotherapy discontinuation cannot be decided before therapy is initiated in patients with advanced colorectal cancer.
本研究比较了在转移性结直肠癌一线治疗中，接受六个周期亚叶酸、氟尿嘧啶和奥沙利铂（FOLFOX）化疗后，停止化疗与用亚叶酸和氟尿嘧啶进行维持治疗的效果。
202例未经治疗的转移性结直肠癌患者被随机分配，一组接受六个周期的改良FOLFOX7（mFOLFOX7），随后接受简化亚叶酸加推注和持续输注氟尿嘧啶直至病情进展（第1组或维持治疗组，n = 98）；另一组在完全停止化疗前接受六个周期的mFOLFOX7（第2组或无化疗间期[CFI]组，n = 104）。两组均计划在肿瘤进展后重新引入mFOLFOX7。主要研究终点是疾病控制持续时间（DDC）。
分配到维持治疗组的患者中位DDC为13.1个月，分配到CFI组的患者为9.2个月（P = 0.046）。维持治疗组的中位无进展生存期（PFS）和总生存期分别为8.6个月和23.8个月，CFI组分别为6.6个月和19.5个月。维持治疗（第1组）和CFI（第2组）的中位持续时间分别为4.8个月和3.9个月。初始FOLFOX化疗的总体缓解率在第1组和第2组分别为59.2%和59.6%，重新引入FOLFOX后的总体缓解率分别为20.4%和30.3%。
与维持治疗策略相比，计划完全停止化疗对DDC和PFS有负面影响。这些结果表明，在晚期结直肠癌患者开始治疗前不能决定停止化疗。
