Wright Heather N, Tosteson Tor D, Hourdequin Kathryn C, Ripple Gregory H, Fuld Alexander D, Dragnev Konstantin H, Amin Manik, Muralikrishnan Sivraj, McGrath Elizabeth B, Stannard Maureen G, Schofield Lora L, Lord-Halvorson Sierra, Tosteson Anna N A, Brooks Gabriel A
Dartmouth Cancer Center, 1 Medical Center Drive, Lebanon, NH, 03756, USA.
Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.
Support Care Cancer. 2025 Aug 8;33(9):769. doi: 10.1007/s00520-025-09784-0.
Unplanned delays are common during FOLFOX chemotherapy. We evaluated a novel FOLFOX dose modification algorithm designed to reduce unplanned delays while maintaining dose intensity.
We conducted a pragmatic, single-arm clinical trial to evaluate PAGODA, a proactive graduated dose modification algorithm for FOLFOX chemotherapy (NCT04526886). The algorithm prescribes chemotherapy dose reductions and delays based on absolute neutrophil count (ANC) and platelet count. Patients receiving FOLFOX-based chemotherapy were eligible. Participants received standard chemotherapy doses in cycle 1 (bolus 5-FU 400 mg/m, oxaliplatin 85 mg/m, and infusional 5-FU 2400 mg/m/46 h). The primary outcome was unplanned delay prior to cycle 6 (> 18 days between cycles). We compared the incidence of unplanned delay against the historical proportion of 43%. Relative dose intensity (RDI) was a key secondary outcome.
There were 48 evaluable participants. The median age was 66, and 50% were female. The most common primary cancer sites were colorectal (n = 31) and gastroesophageal (n = 12). Sixteen of 48 subjects had any unplanned delay before completing cycle 6 (33%, 95% CI 0.22-0.47, p = 0.18 for comparison with the historical proportion) and seven subjects had any cytopenia-related delay (15%, CI 0.07-0.27). Seven cycles were delivered without delay with an ANC of 750-999/µl. The mean chemotherapy RDIs were: oxaliplatin, 86%; infusional 5-FU, 92%; and bolus 5-FU, 65%.
The PAGODA dose modification algorithm was safe and was associated with a low rate of cytopenia-related delays. Further intervention refinement and testing may help to reduce unplanned delays and attendant time toxicity.
Registered at ClinicalTrials.gov on August 21, 2020.
gov ID: NCT04526886.
在FOLFOX化疗期间，计划外延迟很常见。我们评估了一种新型的FOLFOX剂量调整算法，旨在减少计划外延迟，同时维持剂量强度。
我们开展了一项务实的单臂临床试验，以评估PAGODA，这是一种用于FOLFOX化疗的前瞻性分级剂量调整算法（NCT04526886）。该算法根据绝对中性粒细胞计数（ANC）和血小板计数来规定化疗剂量的减少和延迟。接受基于FOLFOX化疗的患者符合条件。参与者在第1周期接受标准化疗剂量（推注5-氟尿嘧啶400mg/m²、奥沙利铂85mg/m²以及持续输注5-氟尿嘧啶2400mg/m²/46小时）。主要结局是第6周期之前的计划外延迟（周期之间间隔>18天）。我们将计划外延迟的发生率与43%的历史比例进行了比较。相对剂量强度（RDI）是关键的次要结局。
有48名可评估的参与者。中位年龄为66岁，50%为女性。最常见的原发癌部位是结肠直肠癌（n = 31）和胃食管癌（n = 12）。48名受试者中有16名在完成第6周期之前出现了任何计划外延迟（33%，95%置信区间0.22 - 0.47，与历史比例比较p = 0.18），7名受试者出现了任何与血细胞减少相关的延迟（15%，置信区间0.07 - 0.27）。7个周期在ANC为750 - 999/µl时无延迟给药。化疗的平均RDI分别为：奥沙利铂86%；持续输注5-氟尿嘧啶92%；推注5-氟尿嘧啶65%。
PAGODA剂量调整算法是安全的，且与血细胞减少相关延迟的发生率较低相关。进一步的干预优化和测试可能有助于减少计划外延迟及伴随的时间毒性。
于2020年8月21日在ClinicalTrials.gov注册。
gov标识符：NCT04526886。
