Could a reduced dose of m FOLFORINOX represent safe and efficacious start-off in advanced pancreatic cancer? A retrospective evaluation of real-world data

Modified FOLFORINOX has improved the outcome of advanced cancer pancreas but with higher toxicity despite being restricted to patients with performance status 0-1 which does not always guarantee treatment tolerability. The palliative treatment intent prioritizes the quality of life and avoidance of hospital admission. The dearth of objective predictive markers for treatment tolerability conceptualizes the safer approach of dose reduction with questionable efficacy.

This retrospective study included advanced cancer pancreas patients received first line m FOLFORINOX in the period from 2018- 2022 at Weston Park Cancer Centre, Sheffield Teaching Hospitals, UK. We excluded patients received neoadjuvant m FOLFORINOX or followed by local radiotherapy. The analysis included clinical features, blood parameters at the first cycle, the number of cycles received, dose reduction, hospital admission secondary to chemotherapy toxicity, 1st PFS, and OS.

The analysis included 104 patients; 44 females (42.3%) and 60 males (57.7%). The mean age was 60.5 years (SD +/-8.552). The mean number of total cycles received was 7.2 (SD+/-5.6), and the mean number of cycles given ot 100% dose was 2.8 (SD+/- 3.3). 74 patients (71.2%) had a reduced dose of the three drugs, the mean dose received after reduction was 80% (16.8 SD+/-), and the mean number of reduced cycles was 4.3 cycles (SD +/- 5.29). 26% of the patients had the first cycle at a reduced dose, and 28% had a dose reduction in the second cycle. Out of patients who had the first cycle at a full dose; 40% failed to have more m FOLFORINOX versus 13.5% in patients who started at a reduced dose which was statistically significant ( p 0.004). Dose reduction was associated with a 14 % higher number of completed cycles ( p 0.007), (OR 1.14) (95% CI 1.03-1.26). The hospital admission rate secondary to chemotherapy-related toxicity was (29.8%) however, (19.2%) followed the first cycle. The statistically significant difference in the hospital admission rate at the first cycle favored the reduced-dose treatment over the full-dose: 13% versus 33% ( p 0.02). There was a moderate negative correlation between the total number of cycles received at 100% dose and the lymphocyte/neutrophil ratio (r -0.48) and a weak positive correlation with the albumin level at the 1st cycle ( r + 0.26). There was no correlation with the weight, BSA, HB, platelet, creatine clearance, or CA19.9. There was no significant difference between the median progression-free survival when early dose reduction was applied compared to patients who received at least 3 cycles at 100% dose; 4 months (SE 0.88 95%CI 2.27-5.72) compared to 6 months (SE 0.95 95%CI 4.12-7.87) ( p 0.13),(HR 0.75 95%CI 0.49-1.13). Also, the median OS in the early dose reduction cohort was 9 months (SE 1.11 95%CI 6.80-11.19) compared to 10 months (SE 1.15 95%CI 6.94-13.05) with 3 cycles or more at 100% dose ( p 0 .96), HR (p 0 .99, HR 0.99 95%CI 0.60-1.64).

Dose reduction of m FOLFORINOX seems safe and reasonable with comparable survival outcome. The level of lymphocyte/neutrophil ratio could be a promising predictive marker, but more research is needed.

The authors.

Has not received any funding.

J. Wadsley: Disclosures not submitted. All other authors have declared no conflicts of interest.