FOLFIRINOX May Be Feasible in Select Elderly Patients With PDAC

A new observational study in the Journal of Clinical Oncology - Oncology Practice provides real-world evidence demonstrating feasibility of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX; FFX) chemotherapy in carefully selected elderly patients with pancreatic ductal adenocarcinoma (PDAC).¹

The retrospective study, which aimed to explore the tolerability of the regimen in a consistently underrepresented group in clinical trials, characterizes the safety profile of FFX among 142 patients older than 70 years of age with metastatic or nonmetastatic PDAC. The most common grade ≥3 adverse events in the overall cohort were infections (26%), nausea/vomiting (22%), diarrhea (18%), anorexia (17%), peripheral neuropathy (17%), and thrombocytopenia (14%). There were 2 treatment-related deaths, both of which were patients with metastatic PDAC.

The study goes on to identify clinical factors associated with toxicity. Factors associated with increased toxicity included metastatic status (odds ratio [OR], 2.41; 95% CI, 1.04–5.62; P =.0409) and psychiatric comorbidities (OR, 6.96; 95% CI, 1.19–40.80; P =.0315), while cardiovascular disease (OR, 0.35; 95% CI, 0.14–0.90; P =.0294) and previous cancer history (OR, 0.22; 95% CI, 0.05–0.89; P =.0335) were associated with decreased toxicity.

Of note, undergoing a multidimensional geriatric assessment (MGA) was associated with reduced toxicity in patients with nonmetastatic PDAC who had a G8 score ≤14 at diagnosis (OR, 0.05; 95% CI, 0–0.49; P =.0103).

Survival Outcomes

The median overall survival (OS) of the entire cohort was 18.3 months (95% CI, 13.8–22.1). A key finding from the survival analysis is that early toxicity within the first month of treatment was significantly associated with worse OS (P =.028). This association persisted through the second month (P =.022).

Implications for Clinical Practice

While FFX is the standard of care in PDAC, FFX is not generally used for older patients due to toxicity and limited evidence in this age group. The authors conclude that FFX can be feasible for certain patients—particularly those who had good ECOG performance—though toxicities remain a concern.

“In carefully selected elderly patients, FFX is feasible, with survival and toxicity outcomes comparable with younger populations,” Collineau et al, study authors, concluded.¹

Importantly, the study suggests that traditional geriatric screening tools may help identify those more vulnerable to FFX toxicity, and that integrating MGA and early supportive care may help reduce toxicities and enhance outcomes. In this study, MGA included consultations with a nurse, dietitian, psychologist, and geriatric oncologist, plus a standardized assessment consisting of mini psychiatric, nutritional, and lifestyle assessments. For oncologists and multidisciplinary teams, these findings reinforce that age alone should not automatically preclude consideration of FFX; instead, individualized patient evaluation should guide treatment decisions for this population.

“Future prospective trials incorporating FFX, MGA, and nutritional support in elderly patients with PDAC are warranted to refine treatment strategies in this growing population,” the authors added.¹

In a corresponding editorial article, Ramy Sedhom, MD and Efrat Dotan, MD of the University of Pennsylvania Health System provided commentary on the study, placing the findings in the broader context of treating older adults with PDAC. While the authors call attention to the inherent design and data limitations of the retrospective study that warrant caution in interpreting results, they emphasized that the study adds critical insights on the “tension between efficacy and tolerability.”

“At first glance, Collineau’s findings seem to be predictable: [FFX] is toxic, and [older adults] are vulnerable. But the deeper issue is whether we are asking the right question,” Sedhom and Dotan wrote.² “By focusing narrowly on which [older adult] can endure [FFX], we risk missing the more relevant point: what is the most tolerable approach to the care of [older adults] with PDAC, and who truly benefits?”

Patient Characteristics and FFX Treatment

The study retrospectively analyzed data of patients treated at the Paoli-Calmettes Cancer Center in France. Patients were included if they were older than 70 years of age, had histologically confirmed borderline, locally advanced, or metastatic PDAC, and were treated with at least 1 FFX course as first-line PDAC treatment between 2011 and 2022; adjuvant FFX cases were excluded.

Of the 142 total patients, 73 had metastatic PDAC and 69 had nonmetastatic PDAC. The median age of the cohort was 74.3 years, and slightly less than half (43%) were aged 75 years and older. Common comorbidities included cardiovascular diseases (60%) and diabetes (25%). Malnutrition was also prevalent in the cohort, with 39% having severe malnutrition and 86% with low muscle mass. Thirty-six patients received enteral or parenteral nutritional support.

Regarding treatment, patients were administered the standard dosing of FFX for 2-week cycles: oxaliplatin at 85mg/m² and leucovorin at 400 mg/m² over 2 hours, irinotecan ag 180mg/m² over 90 minutes, and 5-fluorouracil over 46 hours. Each cycle was followed up with granulocyte colony-stimulating factor (filgrastim or pegfilgrastim). The median FFX cycles received was 4 (range, 1–15). More than half of patients (69%) had primary dose reductions upon FFX initiation.

REFERENCES

1. Collineau B, Bannier-Braticevic C, Gilhodes J, et al. Factors associated with toxicity of FOLFIRINOX in elderly patients with pancreatic ductal adenocarcinoma. JCO Oncol Pract. Published online December 15, 2025:OP2500358-OP2500358. doi:10.1200/op-25-00358

2. Sedhom R, Dotan E. Prioritizing benefit over tolerance among older adults with pancreatic cancer. JCO Oncol Pract. Published online December 15, 2025:OP2500980-OP2500980. doi:10.1200/op-25-00980