Dahan Laetitia, Williet Nicolas, Le Malicot Karine, Phelip Jean-Marc, Desrame Jérôme, Bouché Olivier, Petorin Caroline, Malka David, Rebischung Christine, Aparicio Thomas, Lecaille Cédric, Rinaldi Yves, Turpin Anthony, Bignon Anne-Laure, Bachet Jean-Baptiste, Seitz Jean-François, Lepage Come, François Eric
Department of Digestive Oncology, La Timone, Aix Marseille Université, Marseille, France.
Hepatogastroenterology Department, University Hospital of Saint-Etienne, Saint-Etienne, France.
J Clin Oncol. 2021 Oct 10;39(29):3242-3250. doi: 10.1200/JCO.20.03329. Epub 2021 Jul 21.
Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4-ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC.
In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months.
Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively).
Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.
转移性胰腺癌（mPC）的预后仍然很差。我们之前的试验（PRODIGE 4-ACCORD 11）表明，氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂（FOLFIRINOX）进行6个月化疗在总生存期方面优于吉西他滨。奥沙利铂相关的高限制性神经毒性支持对mPC中奥沙利铂的间歇性给药策略和序贯策略进行评估。
在这项II期研究中，患者被随机分配接受6个月的FOLFIRINOX治疗（A组）、4个月的FOLFIRINOX治疗，随后对病情得到控制的患者采用亚叶酸钙加氟尿嘧啶维持治疗（B组），或每2个月交替使用吉西他滨与氟尿嘧啶、亚叶酸钙和伊立替康的序贯治疗（C组）。主要终点是6个月时的无进展生存期。
2015年1月至2016年11月期间，共纳入276例患者（平均年龄：63岁；范围：40 - 76岁）（A组91例、B组92例、C组90例）。A组10.2%的患者和B组19.8%的患者发生3级或4级神经毒性。A组奥沙利铂的接受剂量/目标剂量的中位数比例为83%，B组为92%。6个月时的无进展生存率A组为47.1%，B组为42.9%，C组为34.1%。A组的中位总生存期为10.1个月，B组为11.2个月，C组为7.3个月。维持治疗组无生活质量评分恶化的中位生存期（11.4个月）高于A组和C组（分别为7.2个月和7.5个月）。
对于诱导化疗4个月后病情得到控制的mPC患者而言，亚叶酸钙加氟尿嘧啶维持治疗似乎可行且有效。维持治疗组的严重神经毒性更高，可能是因为奥沙利铂的累积剂量更高。
