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

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, 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.

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.