de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A
From the Service de Médecine Interne-OncologieHôpital Saint-Antoine, Paris; Debiopharm, Charenton; Service d'Oncologie Médicale, Centre Hospitalier Lyon Sud, Pierre-Benite; and Centre Hospitalier René Dubos, Pontoise, France; Institute of Oncology, Belinson Medical Center, Petach Tikva, Israel; Imperial Cancer Research Fund Cancer Medicine Research Unit, University of Leeds; Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen; Department of Medical Oncology, St Bartholomew's Hospital, London; and Addenbrooke's National Health Service Trust, Cambridge, United Kingdom; Servizio di Oncologia Medica, Arcispedale S. Maria Nuova, Reggio Emilia; Instituto Europeo di Oncologia, Milan; and Clinical Oncology Centre, Service d'Oncologie Médicale, Div Oncologia Medica Azienda, Ospedaliera di Verona, Verona, Italy; Servicio de Oncología, the Hospital 12 de Octubre, Madrid; and Servicio de Onco-Hematologia, Hospital Clinico Universitario, Valencia, Spain.
J Clin Oncol. 2023 Nov 20;41(33):5080-5089. doi: 10.1200/JCO.22.02773.
In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point.
Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m/d) followed by a 5FU bolus (400 mg/m/d) and 22-hour infusion (600 mg/m/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m as a 2-hour infusion on day 1.
Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival (median, 9.0 6.2 months; = .0003) and better response rate (50.7% 22.3%; = .0001) when compared with the control arm. The improvement in overall survival did not reach significance (median, 16.2 14.7 months; = .12). LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia (41.7% 5.3% of patients), grade 3/4 diarrhea (11.9% 5.3%), and grade 3 neurosensory toxicity (18.2% 0%), but this did not result in impairment of quality of life (QoL). Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( = .004).
The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of QoL.
在先前一项针对晚期结直肠癌治疗的研究中，亚叶酸钙（LV）加推注及持续输注氟尿嘧啶（5FU），每2周一次的LV5FU2方案，优于标准的北中部癌症治疗组/梅奥诊所5日推注5FU/LV方案。这项III期研究调查了奥沙利铂与LV5FU2联合应用的效果，将无进展生存期作为主要终点。
420例先前未接受过治疗且有可测量病灶的患者被随机分组，每2周连续2天接受2小时的LV输注（200mg/m²/日），随后是5FU推注（400mg/m²/日）及22小时输注（600mg/m²/日），可单独使用，也可在第1天联合85mg/m²的奥沙利铂进行2小时输注。
与对照组相比，接受奥沙利铂加LV5FU2治疗的患者无进展生存期显著更长（中位数，9.0对6.2个月；P = 0.0003），缓解率更高（50.7%对22.3%；P = 0.0001）。总生存期的改善未达到显著水平（中位数，16.2对14.7个月；P = 0.12）。LV5FU2加奥沙利铂导致美国国立癌症研究所常见毒性标准3/4级中性粒细胞减少（占患者的41.7%对5.3%）、3/4级腹泻（11.9%对5.3%）和3级神经感觉毒性（18.2%对0%）的发生率更高，但这并未导致生活质量（QoL）受损。接受奥沙利铂治疗的患者无疾病进展或总体健康状况恶化的生存期更长（P = 0.004）。
LV5FU2 - 奥沙利铂联合方案作为晚期结直肠癌的一线治疗似乎有益，显示出延长的无进展生存期，具有可接受的耐受性并维持了生活质量。
