A pragmatic, single-arm clinical trial of a dose modification algorithm for preventing cytopenia-related delays during FOLFOX chemotherapy

• Published in: Supportive care in cancer Vol. 33; no. 9; p. 769
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2025; Springer Nature B.V
• Subjects: Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Blood platelets; Blood tests; Cancer therapies; Chemotherapy; Clinical medicine; Clinical trials; Cytopenia - blood; Cytopenia - chemically induced; Cytopenia - prevention & control; Dose-Response Relationship, Drug; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Humans; Internet resources; Leucovorin - administration & dosage; Leucovorin - adverse effects; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasms - blood; Neoplasms - drug therapy; Neutropenia; Neutrophils; Nursing; Nursing Research; Oncology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Oxaliplatin - administration & dosage; Oxaliplatin - adverse effects; Pain Medicine; Patients; Platelet Count; Rehabilitation Medicine; Schedules; Thrombocytopenia; FOLFOX chemotherapy; Unplanned delay; Relative dose intensity
• ISSN: 0941-4355; 1433-7339; 1433-7339
• DOI: 10.1007/s00520-025-09784-0

Purpose Unplanned delays are common during FOLFOX chemotherapy. We evaluated a novel FOLFOX dose modification algorithm designed to reduce unplanned delays while maintaining dose intensity. Methods 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 2 , oxaliplatin 85 mg/m 2 , and infusional 5-FU 2400 mg/m 2 /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. Results 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%. Conclusions 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. Trial registration Registered at ClinicalTrials.gov on August 21, 2020. ClinicalTrials.gov ID: NCT04526886.