Medical Oncology Department, Montpellier Cancer Institute (ICM), University of Montpellier, Montpellier, France; CHU Montpellier, University of Montpellier, Montpellier, France.
Medical Oncology Department, Léon Bérard Centre, Lyon, France.
ESMO Open. 2021 Dec;6(6):100318. doi: 10.1016/j.esmoop.2021.100318. Epub 2021 Nov 24.
Nab-paclitaxel/gemcitabine (AG) and FOLFIRINOX (FFX) are promising drugs in metastatic pancreatic cancer (MPC). This study evaluated a new first-line sequential treatment (AG followed by FFX) in MPC that might overcome resistance to primary therapy and delay tumor progression.
Patients with histologically/cytologically confirmed MPC were included in a multicentric trial receiving AG (day 1, 8 and 15) followed by FFX (day 29 and 43). In phase Ib, three dose-levels were tested for maximum tolerated dose (MTD) and recommended phase II dose. In phase II, the main outcome was the objective response rate (ORR) and secondarily safety, progression-free survival (PFS) and overall survival (OS).
In phase Ib, we included 33 patients (31 assessable) of median age 61.0 years (range 42-75 years) and represented by 54.8% males. Five dose-limiting toxicities were reported without any death. The main grade 3/4 toxicities were neutropenia with spontaneous resolution (35.5%/32.3%), venous thromboembolism (grade 3: 22.6%) and thrombopenia (grade 3: 29.0%), while the MTD was not reached. In phase II, we included 58 patients of median age 60 years (range 34-72 years), 50% males and with Eastern Cooperative Oncology Group stage score 0 and 1 of 37.9% and 62.1%, respectively. They received a median of 4 (1-9) cycles in 8.5 months (0.5-19.8 months). The ORR was 64.9% [95% confidence interval (CI) 51.1% to 77.1%], and neurotoxicity was remarkably low. The main grade 3-4 toxicities were venous thromboembolism, thrombopenia, neutropenia/febrile neutropenia, nausea, diarrhea, weight loss and asthenia without any death. Tumor response was complete in 3.5% and partial in 61.4%, while disease was stable in 19.3% and progressive in 15.8% of patients. The median PFS was 10.5 months (95% CI 6.0-12.5 months) and median OS was 15.1 months (95% CI 10.6-20.1 months).
Sequential AG and FFX showed acceptable toxicity as first-line treatment with no limiting neurotoxicity, while high response rate and survival justify randomized trials.
纳布紫杉醇/吉西他滨（AG）和 FOLFIRINOX（FFX）是转移性胰腺癌（MPC）有前途的药物。本研究评估了一种新的一线序贯治疗（AG 后接 FFX），可能克服对初始治疗的耐药性并延迟肿瘤进展。
组织学/细胞学证实的 MPC 患者纳入多中心试验，接受 AG（第 1、8 和 15 天），然后接受 FFX（第 29 和 43 天）。在 Ib 期，测试了三个剂量水平以确定最大耐受剂量（MTD）和推荐的 II 期剂量。在 II 期，主要终点是客观缓解率（ORR），其次是安全性、无进展生存期（PFS）和总生存期（OS）。
在 Ib 期，我们纳入了 33 名中位年龄 61.0 岁（范围 42-75 岁）的患者（31 名可评估），其中 54.8%为男性。报告了 5 例剂量限制性毒性，但无死亡。主要的 3/4 级毒性为中性粒细胞减少症伴自发性缓解（35.5%/32.3%）、静脉血栓栓塞（3 级：22.6%）和血小板减少症（3 级：29.0%），但未达到 MTD。在 II 期，我们纳入了中位年龄 60 岁（范围 34-72 岁）、50%为男性的 58 名患者，东部合作肿瘤学组（ECOG）分期评分为 0 和 1 的患者分别占 37.9%和 62.1%。他们在 8.5 个月（0.5-19.8 个月）内接受了中位数为 4（1-9）个周期的治疗。ORR 为 64.9%[95%置信区间（CI）为 51.1%至 77.1%]，神经毒性显著降低。主要的 3/4 级毒性为静脉血栓栓塞、血小板减少症、中性粒细胞减少症/发热性中性粒细胞减少症、恶心、腹泻、体重减轻和乏力，无死亡病例。肿瘤完全缓解率为 3.5%，部分缓解率为 61.4%，疾病稳定率为 19.3%，进展率为 15.8%。中位 PFS 为 10.5 个月（95%CI 6.0-12.5 个月），中位 OS 为 15.1 个月（95%CI 10.6-20.1 个月）。
AG 和 FFX 的序贯治疗作为一线治疗具有可接受的毒性，且无限制神经毒性，同时高缓解率和生存率证明了随机试验的合理性。
