Abstract
PURPOSE
For elderly patients with pancreatic ductal adenocarcinoma (PDAC), FOLFIRINOX (FFX) is often contraindicated due to frequent grade III adverse events (AEs) limiting available data on this population.
MATERIALS AND METHODS
This retrospective single-center study identified patients older than70 years treated with FFX for PDAC (2011-2022). Tumor, G8 score calculation (score <14/17 indicates geriatric examination), geriatric, and nutritional parameters were collected. The primary end point was toxicity, defined as grade ≥3 GI AEs or unplanned hospitalization. Overall survival (OS) and toxicity associated factors were analyzed using Cox regression with stepwise selection.
RESULTS
We included 142 patients: 73 with metastatic PDAC (mPDAC) and 69 with non-mPDAC (nmPDAC). Median age was 74 years (71-84), with 43% age 75 years and older. 80% had Eastern Cooperative Oncology Group 0-1. G8 score ≤14 and severe malnutrition were more frequent in mPDAC (82% and 51%) than in nmPDAC (64% and 27%). Low muscle mass was present in >80% of cases. Median FFX exposure was four cycles in mPDAC and 4.5 in nmPDAC. Overall, 56% experienced toxicity, including two treatment-related deaths. Frequent grade ≥3 AEs included infections (26%), nausea/vomiting (22%), and diarrhea (18%). Early toxicity within 2 months was associated with worse OS. Factors linked to toxicity included metastatic status (hazard ratio [HR], 2.41) and psychiatric comorbidities (HR, 6.96), while cardiovascular disease (HR, 0.35) and history of cancer (HR, 0.22) were protective. In nmPDAC, multidimensional geriatric assessment (MGA) reduced toxicity in G8 ≤ 14 patients.
CONCLUSION
FFX is feasible in highly selected elderly patients with PDAC. Severe toxicity remains frequent and proactive supportive care—including MGA in cases of G8 ≤ 14—to avoid early severe toxicity that impact significantly survival.
INTRODUCTION
Pancreatic ductal adenocarcinoma (PDAC) incidence has doubled in 30 years and is projected to become the second leading cause of cancer-related death by 2040.1,2 Prognosis remains poor, partly because of late diagnosis and high prevalence of frailty in patients, most of whom are older than 70 years. Elderly patients often experience malnutrition and comorbidities, and are at risk of undertreatment or overtreatment when frailty is misjudged.3 Functional decline after chemotherapy affects overall survival (OS) in about 20% of patients older than 70 years,3 highlighting the importance of geriatric assessment before treatment initiation. Despite this, older patients remain underrepresented in clinical trials,4 limiting the generalizability of findings in elderly. Aging heterogeneity introduces discrepancies between chronologic age and physiologic age. The G8 screening tool (ONCODAGE),5 an eight-item questionnaire with 76.5% sensitivity for detecting patients needing multidimensional geriatric assessment (MGA), is recommended to screen for vulnerability in those older than 70 years. When altered (score ≤14),6 MGA should assess comorbidities, function, cognition, nutrition, and mood to guide treatment.7-9
CONTEXT
Key Objective
Can FOLFIRINOX (FFX) be safely administered to elderly patients with pancreatic ductal adenocarcinoma (PDAC), and which factors predict toxicity? This study offers real-life data from a large cohort older than 70 years, including patients age 75 years and older, a population underrepresented in trials.
Knowledge Generated
In this retrospective cohort of 142 patients older than 70 years, 56% experienced significant toxicity, and early toxicity correlated with worse overall survival. Psychiatric comorbidities and metastatic status increased toxicity risk, while cardiovascular disease and previous cancer history were protective. In nonmetastatic patients with G8 scores ≤14, multidimensional geriatric assessment (MGA) significantly reduced toxicity.
Relevance
These findings support integrating MGA and early supportive care in elderly patients with PDAC to optimize FFX treatment tolerance and outcomes, and question systematic primary dose reduction without individualized evaluation.
FOLFIRINOX (FFX)—a triplet chemotherapy combining 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and irinotecan—is a standard regimen in metastatic, locally advanced (LA-PDAC), borderline (BL-PDAC), and adjuvant settings.10-14 ASCO and European Society for Medical Oncology recommend restricting FFX to patients younger than 75 years with Eastern Cooperative Oncology Group (ECOG) 0-1 and bilirubin <1.5× normal10 because of its high GI and hematologic adverse events (AEs). Alternative regimens such as gemcitabine with nab-paclitaxel (GNP) or gemcitabine monotherapy are preferred in older or frail patients because of better tolerance but lower efficacy.15,16 Liposomal irinotecan–based regimens are under evaluation.17-19 Most common grade 3-4 AE of FFX are neutropenia, fatigue, diarrhea, and nausea/vomiting (Appendix Table A1, online only). In PRODIGE 4/ACCORD 11, FFX improved quality of life and delayed its deterioration compared with gemcitabine, despite greater toxicity.20
Retrospective studies suggest that with dose adaptation, FFX can be safe and effective in selected elderly patients with advanced or LA/BL-PDAC, with outcomes comparable with younger counterparts.21,22 One study showed that FFX or GNP improved OS and progression-free survival in patients age 65-74 years compared with gemcitabine, while not in those older than 75 years.23 Reported grade ≥3 FFX-related AE in patients older than 70 years vary widely, from 29% to 80%.24-26
This study aimed to evaluate real-life use of FFX in patients older than 70 years and identify factors associated with toxicity.
MATERIALS AND METHODS
Study Design
We conducted a retrospective, single-center study at Paoli-Calmettes Cancer Center (Marseille, France), including consecutive patients older than 70 years who received at least one FFX course as first-line PDAC treatment between 2011 and 2022. Eligible patients had BL/LA-PDAC or metastatic PDAC (mPDAC). Resectable cases treated with upfront surgery were excluded. Infusional 5-FU, leucovorin, and oxaliplatin (FOLFOX) pretreatment (excluding 5-FU bolus) was allowed as stepwise intensification before FFX. All patients had histologically confirmed PDAC. Exclusion criteria included nonadenocarcinoma histology, treatment delivered outside our center, or refusal to share data. Adjuvant FFX cases were excluded because of better prognosis and low numbers in our center.
Data Collection
Patients were identified using ConSoRe (v2022.2.1) (developed by Computer Engineering, Paris, France) enabling electronic medical records mining. Chemotherapy protocols and dose modifications were retrieved via CHIMIOWEB (developed by Computer Engineering, Paris, France) and exported to Excel (developed and distributed by Microsoft Corporation, Redmond, WA). Clinical and laboratory data were manually collected. Toxicities were identified using keyword-based search (eg, “hospitalization,” “anemia,” “neutropenia,” “diarrhea,” “nausea” or “vomiting” etc) and validated manually against clinical notes and laboratory results. Toxicities were graded per Common Terminology Criteria for Adverse Events v5.0.
Nutritional Assessment
Moderate malnutrition was defined by ≥5% weight loss in 1 month, >10% over 6 months, body mass index (BMI) < 22 kg/m2, or sarcopenia. Severe malnutrition was defined by BMI < 20 kg/m2, ≥10% weight loss in 1 month or >15% overall, or albumin ≤30 g/L (HAS 202127). In our study, sarcopenia was inferred from low muscle mass defined as a skeletal muscle index <55.4 cm2/m2 in men and <28.9 cm2/m2 in women, measured at the L3 vertebral level on computed tomography (CT) scans by a radiology technician using Myrian software (developed by Intrasense, Montpellier, France).
Geriatric Assessment and Comorbidities
G8 scores at FFX initiation were available for 50 patients (35%). For the 92 patients with missing G8 scores, 73 were classified as G8 ≤ 14 on the basis of age older than 70 years with weight loss >3 kg. MGA included consultations with a nurse, a dietitian, a psychologist, and a geriatric oncologist, and standardized assessment (mini mental state examination [MMSE], grip strength, mini-nutritional assessment, mini-geriatric depression scale [GDS], timed up and go test, activities of daily living [ADL], Lawton and Brody Instrumental Activities of Daily Living scale [IADL], Lee score, and Hurria score).
Comorbidities (≥10% prevalence) were categorized: cardiovascular (hypertension, coronary artery disease, peripheral vascular disease), pulmonary (chronic obstructive pulmonary disease, pulmonary embolism), psychiatric (depression, anxiety), and previous cancer. Polypharmacy was defined as ≥4 daily medications. Anemia was defined by hemoglobin <11 g/dL.
Chemotherapy Protocol
Each cycle of FFX included the following standard doses: oxaliplatin 85mg/m2 administrered over 2 hours, leucovorin 400 mg/m2 administrered over 2 hours, irinotecan 180mg/m2 administrered over 90 minutes and 5FU administrered over 46 hours. No 5FU bolus was used. Each cycle was repeated every two weeks. All patients received primary granulocyte colony-stimulating factor (G-CSF; filgrastim or pegfilgrastim) after each FFX course.
Statistical Analyses
The primary end point was toxicity, defined as a composite criterion: any grade ≥3 GI AE (reported or leading to hospitalization) or unplanned hospitalization (regardless of the reason). The secondary end point was OS, defined as the time from FFX initiation to death or last follow-up. Patients admitted at hospital for disease progression (ie, hospitalization for disease-related symptoms was excluded from the toxicity analysis).
Quantitative variables are presented by median (range) and categorial as count (%). Odds ratios (ORs) with 95% CIs were calculated using univariable and multivariable logistic regression. Stepwise selection was applied. OS was estimated by using Kaplan-Meier, and median follow-up calculated by using reverse Kaplan-Meier. Cox regression (univariable and stepwise multivariable) identified factors associated with toxicity and OS. Toxicity and dose reduction during treatment were modeled as time-dependent covariates in adjusted models.
All tests were two-sided, and P value <.05 was significant. Analyses were performed using SAS v9.4 and R Statistical Software (version 4.3.2; R Foundation for Statistical Computing, Vienna, Austria).
Ethics Statement
This study was approved by our internal review board under the reference number FFRNX-TOX70-IPC-2021-043.
RESULTS
Baseline Characteristics
Between September 2011 and December 2022, 204 patients were identified. After excluding 62 (treatment outside our center, chemotherapy miscoding, non-PDAC histology, adjuvant cases, duplicates, or incomplete data), 142 patients were included: 73 patients with mPDAC and 69 with non-mPDAC (nmPDAC; Appendix Fig A1).
Median age was 74.3 years (71-84), with 43% of patients age 75 years and older. Most patients (80%) had an ECOG performance status (PS) of 0-1. Metastases were present in 50%, and 47% had an elevated carbohydrate antigen 19-9 level (>500 U/mL).
Among the 40 patients with known G8 score ≤14 at diagnosis, 39 patients underwent a baseline MGA. Considering all patients with G8 ≤ 14 (80% of our cohort), only 34.5% received MGA. Cardiovascular diseases (60%) and diabetes (25%) were the most prevalent comorbidities. Polypharmacy (≥4 medications/day) was observed in 32%. Malnutrition was common: 39% had severe malnutrition and 86% low muscle mass; 24.5% received nutritional support. A total of 36 patients (24.5%) received nutritional support (enteral or parenteral). Severe malnutrition and G8 ≤14 were more frequent in mPDAC than in nmPDAC (51% v 27.5% and 82% v 64%, respectively), whereas MGA was more often performed in patients with nmPDAC (40% v 30%; Table 1).
TABLE 1.
Patients Characteristics (N = 142) and Details Between Groups (mPDAC and nmPDAC)
| Subgroup | All (N = 142) | mPDAC (n = 73) | nmPDAC (n = 69) |
|---|---|---|---|
| Sex, No. (%) | |||
| Male | 69 (49) | 39 (53) | 30 (43.5) |
| Female | 73 (51) | 34 (47) | 39 (56.5) |
| Age, No. (%) | |||
| 71-74 | 81 (57) | 43 (59) | 38 (55) |
| ≥75 | 61 (43) | 30 (41) | 31 (45) |
| PS ECOG, No. (%) | |||
| 0-1 | 113 (80) | 57 (78) | 56 (81) |
| ≥2 | 29 (20) | 16 (22) | 13 (19) |
| CA 19-9,a No. (%) | |||
| <35 | 15 (12) | 5 (8) | 13 (21) |
| 35-500 | 49 (41) | 19 (31) | 31 (49) |
| >500 | 56 (47) | 38 (61) | 19 (30) |
| Malnutrition, No. (%) | |||
| No or moderate | 9 (61) | 36 (49) | 50 (72.5) |
| Severe | 57 (39) | 37 (51) | 19 (27.5) |
| Low muscle mass, No. (%) | |||
| No | 20 (14) | 9 (12) | 11 (16) |
| Yes | 122 (86) | 64 (88) | 58 (84) |
| G8 score, No. (%) | |||
| >14 or NA | 29 (20) | 13 (18) | 27 (36) |
| ≤14 | 113 (80) | 60 (82) | 47 (64) |
| MGA if G8 ≤ 14, No. (%) | |||
| No | 74 (65.5) | 42 (70) | 32 (60) |
| Yes | 39 (34.5) | 18 (30) | 21 (40) |
| Anemia at diagnosis,a No. (%) | |||
| No | 113 (84) | 61 (88) | 37 (53) |
| Yes | 20 (14) | 8 (12) | 14 (47) |
| Polypharmacy,a No. (%) | |||
| No | 92 (68) | 49 (68) | 43 (67) |
| Yes | 44 (32) | 23 (32) | 21 (32) |
| Diabetes mellitus, No. (%) | |||
| No | 106 (75) | 58 (79) | 50 (68) |
| Yes | 36 (25) | 15 (21) | 24 (32) |
| Cardiovascular comorbidity, No. (%) | |||
| No | 57 (40) | 31 (42) | 26 (38) |
| Yes | 85 (60) | 42 (58) | 43 (62) |
| Pulmonary comorbidity, No. (%) | |||
| No | 129 (91) | 65 (89) | 64 (93) |
| Yes | 13 (9) | 8 (11) | 5 (7) |
| Psychiatric comorbidity, No. (%) | |||
| No | 128 (89) | 66 (90) | 62 (90) |
| Yes | 14 (11) | 7 (10) | 7 (10) |
| History of another cancer, No. (%) | |||
| No | 126 (79) | 64 (88) | 62 (90) |
| Yes | 16 (11) | 9 (12) | 7 (10) |
Abbreviations: CA 19-9, carbohydrate antigen 19-9; MGA, multidimensional geriatric assessment; mPDAC, metastatic pancreatic ductal adenocarcinoma; NA, not applicable; nmPDAC, non-mPDAC; PS ECOG, performance status Eastern Cooperative Oncology Group.
NA: CA 19-9 = 22, anemia = 7, polypharmacy = 11.
FFX Administration and Dose Adjustments
Patients received a median of four FFX cycles (range, 1-15). Details on dose adjustments are provided in Appendix Table A2.
Primary dose reductions at FFX initiation were implemented in 69% of patients, affecting irinotecan (63%), oxaliplatin (35%), or 5-FU (10%). 12 patients (8%) started with FOLFOX before escalation to FFX and were considered as having primary dose reduction. Among patients age 71-74 years, initial dose reductions were applied in 60% (mPDAC) and 53% (nmPDAC). In those age 75 years and older, these rates increased to 83% and 84%, respectively, for mPDAC and nmPDAC. Regardless of initial dose, 68% of patients required further dose reductions during treatment. FFX discontinuation due to toxicity occurred in 32% of cases. Oxaliplatin and irinotecan were stopped in 12% (median six cycles) and 21% (median two cycles), respectively.
Figures 1A and 1B show treatment distribution by age group in mPDAC and nmPDAC. In mPDAC, 14 patients (19%) received only one FFX cycle, most frequently in patients age 71-74 years.
FIG 1.
Histogram representing the distribution of cycles depending on groups of age in (A) mPDAC and (B) nmPDAC. mPDAC, metastatic pancreatic ductal adenocarcinoma; nmPDAC, non-mPDAC.
Toxicity Analysis
All 142 patients were assessable for safety (Table 2). The composite toxicity criterion occurred in 56% of cases. The most frequent grade ≥3 AEs were vomiting (22%), diarrhea (18%), anorexia (17%), peripheral neuropathy (17%), and thrombocytopenia (14%). Febrile neutropenia was uncommon (5%). By the end of FFX treatment, 23% of patients had lost 5%-10% of their body weight and 16% had lost >10%. Two treatment-related deaths occurred in patients with mPDAC age 71-74 years, both within 15 days of the last FFX cycle.
TABLE 2.
Description of Safety Under FFX (N = 142)
| Observed Severe AE (N = 142) | No. (%) |
|---|---|
| General | |
| Digestive grade ≥3 AE or unplanned hospitalization | 79 (56) |
| Hospitalization | 66 (47) |
| Death related to SAE (grade 5) | 2 (1) |
| Digestives (grade 3) | |
| Diarrhea | 25 (18) |
| Anorexia | 23 (17) |
| Nausea | 15 (11) |
| Vomiting | 15 (11) |
| Infectious | |
| Infection without aplasia | 37 (26) |
| Febrile neutropenia | 7 (5) |
| Hematologic (grade 3) | |
| Thrombocytopenia | 19 (14) |
| Anemia | 10 (7) |
| Neutropenia | 5 (4) |
| Others | |
| Peripheral neuropathy G3 | 23 (17) |
| Acute kidney injury | 3 (2) |
| Coronary spasm | 1 (<1) |
| Loss of weight (% of body weight) | |
| <5 | 85 (61) |
| 5-10 | 32 (23) |
| >10 | 22 (16) |
Abbreviations: AE, adverse event; FFX, FOLFIRINOX; SAE, serious adverse event.
Toxicity occurring within the first month was significantly associated with shorter OS (P = .028), although no statistical difference in OS was observed between age groups (Appendix Figs A2A and A2B). At 2 months, toxicity remained associated with worse OS (P = .022, Fig 2A). Median OS among patients with toxicity was 10.7 months (5-27) for those age 71-74 years and 12.9 months (9-43) for those age 75 years and older, versus 18.8 (14-47) and 22.6 months (19-31.5), respectively, in patients without toxicity (P = .14, Fig 2B).
FIG 2.
Overall survival according to (A) occurrence of toxicity at 2 months and (B) with comparison between groups of age (71-74 and ≥75 years).
Univariate and multivariable analyses of toxicity in the overall population, mPDAC, and nmPDAC population are detailed in Table 3.
TABLE 3.
Univariate and Multivariable Analyses (after stepwise analysis) for Toxicity in Overall Population, mPDAC, and nmPDAC
| Subgroup | Univariable Analyses | Multivariable Analyses | ||||
|---|---|---|---|---|---|---|
| Overall Population | mPDAC | nmPDAC | Overall Population | mPDAC | nmPDAC | |
| OR (95% CI); P | OR (95% CI); P | OR (95% CI); P | OR (95% CI); P | OR (95% CI); P | OR (95% CI); P | |
| Sex | ||||||
| Female v male | 0.85 (0.44 to 1.66); .6393 | 0.78 (0.30 to 2.03); .6157 | 0.83 (0.32 to 2.16); .7042 | |||
| Age at diagnosis | ||||||
| ≥75 v 71-74 years | 0.90 (0.46 to 1.75); .7492 | 0.55 (0.21 to 1.44); .2246 | 1.50 (0.58 to 3.89); .4046 | 3 (0.50 to 17.91); .2276 | ||
| PS ECOG | ||||||
| ≥2 v 0-1 | 1.68 (0.72 to 3.93); .2326 | 2.18 (0.63 to 7.60); .2204 | 1.25 (0.37 to 4.20); .7151 | |||
| Metastasis | ||||||
| Yes v no | 1.65 (0.85 to 3.22); .1392 | NA | NA | 2.41 (1.04 to 5.62); .0409 | ||
| Malnutrition | ||||||
| Severe v no or moderate | 1.59 (0.80 to 3.16); .1851 | 1.67 (0.64 to 4.32); .2929 | 1.20 (0.42 to 3.47); .7313 | |||
| Low muscle mass | ||||||
| Yes v no | 1.65 (0.64 to 4.26); .3049 | 2.23 (0.54 to 9.13); .2656 | 1.20 (0.33 to 4.38); .7824 | |||
| MGA if G8 ≤ 14 | ||||||
| Yes v no | 0.67 (0.30 to 1.47); .3194 | 0.90 (0.28 to 2.91); .8559 | 0.58 (0.19 to 1.77); .3418 | 0.48 (0.19 to 1.20); .1171 | 0.05 (0 to 0.49); .0103 | |
| Primary dose reduction | ||||||
| Yes v no | 1.22 (0.60 to 2.49); .5893 | 1.17 (0.42 to 3.24); .7684 | 1.25 (0.45 to 3.46); .6643 | |||
| Anemia at diagnosis | ||||||
| Yes v no | 1.19 (0.47 to 3); .7155 | 2.08 (0.39 to 11.17); .3918 | 1 (0.31 to 3.26); 1 | |||
| Polypharmacy | ||||||
| Yes v no | 1.60 (0.77 to 3.36); .2094 | 2.12 (0.72 to 6.32); .1750 | 1.26 (0.44 to 3.60); .6594 | 1.93 (0.74 to 5.02); .1782 | 2.12 (0.72 to 6.32); .1750 | |
| Diabetes mellitus | ||||||
| Yes v no | 1 (0.47 to 2.13); .9913 | 0.65 (0.21 to 2.04); .4595 | 1.58 (0.56 to 4.43); .3887 | 4.90 (0.84 to 28.56); .0774 | ||
| Cardiovascular comorbidity | ||||||
| Yes v no | 0.47 (0.23 to 0.93); .0315 | 1.03 (0.40 to 2.66); .09574 | 0.20 (0.07 to 0.58); .0029 | 0.35 (0.14 to 0.90); .0294 | 0.07 (0.01 to 0.42); .0033 | |
| Pulmonary comorbidity | ||||||
| Yes v no | 1.90 (0.56 to 6.47); .3071 | 2 (0.37 to 10.68); .4175 | 1.60 (0.25 to 10.21); .6210 | |||
| Psychiatric comorbidity | ||||||
| Yes v no | 2.14 (0.64 to 7.17); .2189 | 1.62 (0.29 to 9.01); .5786 | 2.84 (0.51 to 15.79); .2319 | 6.96 (1.19 to 40.84); .0315 | 48.37 (2.59 to 902.18); .0094 | |
| History of another cancer | ||||||
| Yes v no | 0.77 (0.27 to 2.19); .6308 | 0.75 (0.18 to 3.07); .6890 | 0.75 (0.15 to 3.63); .7208 | 0.22 (0.05 to 0.89); .0335 | 0.02 (0 to 0.94); .0463 | |
NOTE. Bold indicates p <0.05 (threshold for statistical significance).
Abbreviations: MGA, multidimensional geriatric assessment; mPDAC, metastatic pancreatic ductal adenocarcinoma; NA, not applicable; nmPDAC, non-mPDAC; OR, odds ratio; PS ECOG, performance status Eastern Cooperative Oncology Group.
In overall population, metastatic disease (OR, 2.41 [1.04 to 5.62]; P = .0409) and psychiatric comorbidities (OR, 6.96 [1.19 to 40.80]; P = .0315) were significantly associated with increased toxicity. Conversely, cardiovascular comorbidities (OR, 0.35 [0.14 to 0.90]; P = .0294) and previous cancer history (OR, 0.22 [0.05 to 0.89]; P = .0335) were associated with reduced toxicity. MGA in patients with a G8 score ≤14 (OR, 0.48 [0.19 to 1.20]; P = .1171) and polypharmacy (OR, 1.93 [0.74 to 5.02]; P = .1782) were retained in the stepwise analysis but did not reach statistical significance. Other tested variables included age, sex, ECOG PS, malnutrition, low muscle mass, initial dose reduction, anemia, and pulmonary comorbidities.
Subgroup Analysis
In mPDAC, only polypharmacy (OR, 2.12 [0.72 to 6.32]; P = .1750) was retained in stepwise analysis, without statistical significance.
In nmPDAC, reduced toxicity was associated with MGA in G8 ≤ 14 patients (OR, 0.05 [0 to 0.49]; P = .0103), cardiovascular comorbidities (OR, 0.07 [0.01 to 0.42]; P = .0033), and previous cancer (OR, 0.02 [0 to 0.94]; P = .0463). Increased toxicity was linked to psychiatric comorbidities (OR, 48.37 [2.59 to 902.18]; P = .0094). Age 75 years and older (OR, 3 [0.50 to 17.91]; P = .2276) and diabetes (OR, 4.90 [0.84 to 28.56]; P = .0774) were retained in stepwise analysis but not significant.
Survival Analysis
The median OS for the entire cohort was 18.3 months (13.8-22.1), with 1-, 2-, and 4-year survival rates of 64%, 39%, and 18%, respectively. No significant OS difference was observed between age groups: median OS was 12 months in patients age 71-74 years versus 15 months in those age 75 years and older (P = .43, Fig 3).
FIG 3.
Overall survival according to groups of age (71-74 and ≥75 years).
Univariate and multivariable analyses of OS in the overall population, mPDAC, and nmPDAC cohorts are presented in Table 4.
TABLE 4.
Univariable and Multivariable Analyses (after stepwise analysis) for Overall Survival in Overall Population, mPDAC, and nmPDAC
| Subgroup | Univariable Analyses | Multivariable Analyses | ||||
|---|---|---|---|---|---|---|
| Overall Population | mPDAC | nmPDAC | Overall Population | mPDAC | nmPDAC | |
| HR (95% CI); P | HR (95% CI); P | HR (95% CI); P | HR (95% CI); P | HR (95% CI); P | HR (95% CI); P | |
| Sex | ||||||
| Female v male | 0.51 (0.35 to 0.75); <.001 | 0.44 (0.26 to 0.74); .002 | 0.58 (0.32 to 1.06); .078 | 0.44 (0.29 to 0.67); .0001 | 0.42 (0.24 to 0.73); .0022 | |
| Age at diagnosis | ||||||
| ≥75 v 71-74 years | 1.14 (0.78 to 1.67); .498 | 1.36 (0.82 to 2.25); .231 | 1 (0.55 to 1.81); .992 | |||
| PS ECOG | ||||||
| ≥2 v 0-1 | 1.15 (0.72 to 1.84); .568 | 1.14 (0.65 to 2.02); .648 | 0.98 (0.41 to 2.35); .957 | |||
| Metastasis | ||||||
| Yes v no | 1.83 (1.25 to 2.68); .002 | NA | NA | 1.73 (1.16 to 2.59); .0077 | NA | NA |
| Malnutrition | ||||||
| Severe v no or moderate | 1.03 (0.71 to 1.50); .880 | 0.75 (0.46 to 1.21); .232 | 1.12 (0.59 to 2.16); .725 | |||
| Low muscle mass | ||||||
| Yes v no | 1.26 (0.73 to 2.18); .402 | 0.72 (0.34 to 1.53); .388 | 2.03 (0.85 to 4.85); .113 | |||
| G8 ≤ 14 | ||||||
| Yes v no | 0.84 (0.42 to 1.68); .626 | 1.04 (0.41 to 2.61); .938 | 0.64 (0.23 to 1.82); .403 | |||
| Primary dose reduction | ||||||
| Yes v no | 1.56 (1.02 to 2.39); .041 | 1.38 (0.81 to 2.35); .242 | 1.87 (0.90 to 3.87); .092 | 1.66 (1.04 to 2.67); .0340 | 1.51 (0.84 to 2.72); .1696 | |
| Toxicity | ||||||
| Yes v no | 1.38 (0.94 to 2.03); .0955 | 1.67 (1 to 2.76); .0482 | 0.94 (0.51 to 1.74); .8432 | 1.60 (1.06 to 2.41); .0257 | 1.77 (1.01 to 3.10); .0449 | 1.84 (0.84 to 4.04); .1262 |
| Surgery | ||||||
| Yes v no | NA | NA | 0.28 (0.14 to 0.58); <.001 | NA | NA | 0.16 (0.05 to 0.45); .0006 |
| Radiotherapy | ||||||
| Yes v no | NA | NA | 1.15 (0.62 to 2.16); .653 | NA | NA | 0.41 (0.17 to 0.98); .0442 |
NOTE. Bold indicates p <0.05 (threshold for statistical significance).
Abbreviations: HR, hazard ratio; mPDAC, metastatic pancreatic ductal adenocarcinoma; NA, not applicable; nmPDAC, non-mPDAC; PS ECOG, performance status Eastern Cooperative Oncology Group.
In overall population, female gender (hazard ratio [HR], 0.44 [0.29 to 0.67]; P = .0001) was significantly associated with improved OS, while metastases (HR, 1.73 [1.16 to 2.59]; P = .0077), primary dose reduction (HR, 1.66 [1.04 to 2.67]; P = .0340), and occurrence of toxicity (HR, 1.60 [1.06 to 2.41]; P = .0257) were associated with worse OS.
Subgroup Analysis
In mPDAC, median OS was 12.8 months (9.8-14.8). Female gender remained protective (HR, 0.42 [0.24 to 0.73]; P = .0022), while toxicity was associated with shorter OS (HR, 1.77 [1.01 to 3.10]; P = .0449). Primary dose reduction was not significant (HR, 1.51 [0.84 to 2.72]; P = .1696).
In nmPDAC, median OS was 24.8 months (18.8-35.3). Surgery (HR, 0.16 [0.05 to 0.45]; P = .0006) and radiotherapy (HR, 0.41 [0.17 to 0.98]; P = .046) were associated with improved OS. Toxicity was retained in stepwise analysis but not significant (HR, 1.84 [0.84 to 4.04]; P = .1262).
DISCUSSION
Because of its toxicity and limited evidence in older adults, FFX is not standard for patients with PDAC older than 75 years. In practice, its use is typically restricted to highly selected patients with dose adjustments, on the basis of data extrapolated from younger populations.
Here, we analyzed 142 patients older than 70 years, including 43% age 75 years and older, treated for BL-PDAC, LA-PDAC, or mPDAC. This large real-world cohort provides insight into FFX tolerance and survival in this population.
Most patients were selected by experienced oncologists on the basis of ECOG PS and comorbidities, with frequent upfront dose reductions. Interestingly, median OS did not differ significantly between patients age 71-74 years and those age 75 years and older, although toxicity appeared more frequent in patients age 75 years and older with nmPDAC, highlighting the importance of careful selection and follow-up. These findings align with previous studies reporting similar grade ≥3 toxicity rates across age groups.26,28 Our results are also consistent with a subgroup analysis from the NAPOLI-3 trial including patients older than 70 years.29 Our results support the feasibility of FFX in selected elderly patients with advanced-stage PDAC, with outcomes comparable with younger cohorts.24,26,28
Despite national guidelines recommending use of G8 scores for patients older than 75 years,30 data were missing for 25% of such patient. Among those assessed, 84% (71-74 years) and 80% (age 75 years and older) in the mPDAC group had G8 ≤ 14, compared with 71% and 87%, respectively, in nmPDAC. Retrospective G8 scoring may have been skewed by weight loss. Notably, only 34.5% of patients with a G8 score ≤14 ultimately underwent an MGA, highlighting the challenges of integrating geriatric pathways even in expert centers.
Severe malnutrition affected nearly 40% of patients, a known poor prognostic factor in cancer patients older than 70 years.31 Although its prognostic value in PDAC patients age 75 years and older remains unclear, its relevance is supported in other solid tumors.32 Low muscle mass was reported in 86% of patients, on the basis of CT at L3. Although EWGSOP recommends other methods for sarcopenia assessment,33 CT analysis is increasingly used because of its availability and objectivity. Its clinical value is supported by data from colorectal cancer (eg, LEANOX study), suggesting lean body mass–based dosing may reduce neurotoxicity.34 Early detection and supportive care, including nutrition and physical activity, should thus be systematically integrated in elderly PDAC care.
We observed 69% of primary dose reductions, mostly of irinotecan, consistent with previous reports (57%-75%).24,35 Surprisingly, dose reduction did not prevent toxicity and was associated with worse OS, particularly in mPDAC. Although dose adjustment is often used to reduce hospitalization risk,36 it should ideally be guided by standardized approaches such as MGA rather than age or physician judgment alone.
We used a composite definition of toxicity, combining grade ≥3 GI AEs and unplanned hospitalizations due to AE. This reflects the true clinical burden in elderly patients, as hospitalization often leads to functional decline.37,38 Peripheral neuropathy was excluded from the composite criterion, as it is rarely life-threatening, although it affects quality of life.
FFX-related grade ≥3 toxicities varied widely across studies (29%-80%) in elderly patients.35,39 In our study, febrile neutropenia was low (5%), likely because of prophylactic G-CSF and the omission of 5-FU bolus, as in NAPOLI-3 and PRODIGE-24.12,19 Hospitalization rates were comparable with other series in patients age 65 years and older.23
Few studies guide the selection of elderly candidates for FFX. In our analysis, MGA in patients with G8 ≤ 14 was associated with lower toxicity in nmPDAC, echoing findings from the GAP70+ trial, where MGA-driven interventions reduced chemotherapy-related toxicity.40 We advocate for systematic use of G-CSF and preemptive nutritional and metabolic evaluation to anticipate complications and guide dosing.
Interestingly, cardiovascular comorbidities and previous cancer history were associated with less toxicity, possibly reflecting closer follow-up or enhanced supportive care. By contrast, psychiatric comorbidities—particularly depression—were strongly associated with increased toxicity. This aligns with literature linking depression to altered immunity and heightened vulnerability to treatment-related AEs in older adults.39
OS in our cohort was consistent with published data for both mPDAC and nmPDAC.10,41 As expected, metastatic disease was associated with poorer OS. Notably, both toxicity and primary dose reduction had a negative impact on survival, reinforcing the importance of appropriate patient selection and supportive care. Female gender was associated with improved OS, an observation rarely explored in PDAC. In our study, women had less low muscle mass (77% v 96%) and fewer altered G8 scores (76% v 84%), despite slightly higher rates of severe malnutrition (41% v 37%).
In nmPDAC, surgery and radiotherapy were both associated with improved OS. Surgical resection is well established as a major prognostic factor in resectable or BL-PDAC.5,6 By contrast, radiotherapy has shown inconsistent survival benefits in prospective trials, but may be preferred over surgery in patients with anesthetic contraindications.42 In our cohort, surgery rates were in line with those reported for BL-PDAC, but lower in LA-PDAC, where radiotherapy may have been chosen instead.14
The impact of our conclusions must be balanced by several limitation. The retrospective analysis could generate selection bias, and we tried to reduce missing data. Moreover, toxicity evaluation could have been affected by synchronous symptoms associated to disease aggressiveness. A key limitation of our study was the lack of specific data regarding nutritional and physical interventions, which should be addressed in future prospective studies. We also had limited data about social and geriatric scale evaluation (MMSE, ADL/IADL, grip test) because of a small number of patients who have underwent MGA. Those limitations tend to reduce the benefit of a personalized and multimodal intervention for frail/elderly patients receiving FFX that should be reported in further analysis.
Supportive strategies should be prioritized during the first 2 months of treatment, a critical period during which early toxicity appears to affect survival independently of disease progression. Indeed, early toxicity often leads to treatment interruption or dose reduction after only one to two cycles, reducing overall dose intensity and potentially impairing outcomes. These early events may act as surrogate markers for long-term prognosis. Preventing early toxicity through optimized nutrition, close follow-up, and tailored chemotherapy could improve outcomes. Prospective trials combining FFX with MGA and nutritional interventions in elderly patients are needed to validate these findings.
In conclusion, in carefully selected elderly patients, FFX is feasible, with survival and toxicity outcomes comparable with younger populations. In mPDAC, where the intent is palliative, primary dose reduction may be appropriate. However, in nmPDAC, where the objective is curative, full-dose regimens should be prioritized when possible.
Early toxicity, particularly within the first 2 months, is associated with reduced survival and may serve as a surrogate marker for prognosis. Systematic use of MGA and early supportive interventions is essential to anticipate and mitigate toxicities. Future prospective trials incorporating FFX, MGA, and nutritional support in elderly patients with PDAC are warranted to refine treatment strategies in this growing population.
ACKNOWLEDGMENT
The authors thank the patients and their families. The authors also thank GIRCI for providing funding for the study. Some parts of the text have been edited for English clarity by ChatGPT-4o (OpenAI).
APPENDIX
FIG A1.
Flowchart of population. FFX, FOLFIRINOX; mPDAC, metastatic pancreatic ductal adenocarcinoma; nmPDAC, non-mPDAC.
FIG A2.
Overall survival according to (A) occurrence of toxicity at 1 month and (B) with comparison between groups of age (71-74 and ≥75 years).
TABLE A1.
Grade 3-4 AE in the Main Studies That Evaluated Combination With 5-FU, Oxaliplatin, and Irinotecan/Nal-Irinotecan 10,12,17,19
| Subgroup | PRODIGE 4/ACCORD 11 | PRODIGE 24 | NAPOLI-3 | GIANT |
|---|---|---|---|---|
| FOLFIRINOX | FOLFIRINOX | NALIRIFOX | Naliri + 5-FU | |
| Conroy et al10 | Conroy et al12 | Wainberg et al19 | Dotan et al17 | |
| No = 171 | No = 238 | No = 370 | No = 88 | |
| Elderly ≥70 years, % | NA | NA | 28 | 100 |
| All grade 3-4, % | NA | 75.9 | 87 | |
| >70 years grade 3-4, % | NA | NA | 87 | 58 |
| Hematologic, % | ||||
| Anemia | 7.8 | 3.4 | 11 | 13 |
| Thrombocytopenia | 9.1 | 1.3 | 1 | 5 |
| Neutropenia | 45.7 | 28.4 | 14 | 20 |
| Febrile neutropenia | 5.4 | 3 | 2.4 | NA |
| Nonhematologic, % | ||||
| Fatigue/asthenia | 23.6 | 11 | 15 | 15 |
| Nausea | NA | 5.5 | 12 | 7 |
| Vomiting | 14.5 | 5.1 | 7 | 4 |
| Diarrhea | 12.7 | 18.6 | 20 | 12 |
| Sensitive neuropathy | 9 | 9.3 | 6.7 | 0 |
| ALAT increased | 7.3 | 4.2 | 3.5 | NA |
| Thromboembolism | 6.6 | 2.5 | 5.7 | NA |
Abbreviations: 5-FU, 5-fluorouracil; AE, adverse event; ALAT, alanine aminotransferase; NA, not applicable.
TABLE A2.
Description of Dose Adjustment for FFX in mPDAC and nmPDAC
| Subgroup | Total (N = 142) | Metastatic Group (mPDAC) | Nonmetastatic Group (nmPDAC) | ||
|---|---|---|---|---|---|
| 71-74 Years (n = 43) | ≥75 Years (n = 30) | 71-74 Years (n = 38) | ≥75 Years (n = 31) | ||
| Number of cycles | 5 (1-15) | 4 (1-12) | 4.5 (1-12) | 5 (1-10) | |
| Primary dose reduction, No. (%) | |||||
| No | 44 (31) | 17 (40) | 5 (17) | 18 (47) | 5 (16) |
| Yes | 98 (69) | 26 (60) | 25 (83) | 20 (53) | 26 (84) |
| Reduction dose during courses, No. (%) | |||||
| No | 45 (32) | 14 (33) | 8 (27) | 10 (26) | 13 (42) |
| Yes | 98 (68) | 29 (67) | 22 (73) | 28 (74) | 18 (58) |
| Discontinuation of one drug, No. (%) | |||||
| No | 96 (68) | 28 (65) | 17 (57) | 30 (79) | 20 (65) |
| Yes | 46 (32) | 15 (35) | 13 (43) | 8 (21) | 11 (35) |
| Number of cycles, No. (%) | |||||
| 1-4 | 72 (51) | 21 (49) | 18 (60) | 19 (50) | 14 (45) |
| ≥5 | 70 (49) | 22 (51) | 12 (40) | 19 (50) | 17 (55) |
Abbreviations: FFX, FOLFIRINOX; mPDAC, metastatic pancreatic ductal adenocarcinoma; nmPDAC, non-mPDAC.
Céline Delaunay
Honoraria: Pierre Fabre
Travel, Accommodations, Expenses: Fresenius Kabi
Philippe Rochigneux
Honoraria: AstraZeneca, Novartis (Inst), Bristol Myers Squibb Foundation (Inst), Viatris, Roche
Research Funding: Novartis (Inst), AstraZeneca (Inst)
Travel, Accommodations, Expenses: Pfizer, Roche
Christelle de la Fouchardière
Consulting or Advisory Role: Bristol Myers Squibb, Amgen, Servier, Pierre Fabre, MSD Oncology, Roche/Genentech, Daichi-Sankyo, Astellas Pharma, Gilead Sciences, BeiGene, Jazz Pharmaceuticals, Takeda, AbbVie, AstraZeneca
Research Funding: Pierre Fabre (Inst), Servier (Inst), MSD (Inst), Agenus (Inst)
Travel, Accommodations, Expenses: Pierre Fabre, Servier, MSD Oncology, Amgen, AstraZeneca
Emmanuel Mitry
Honoraria: Pierre Fabre, AstraZeneca/Daiichi Sankyo, Servier, Esteve, MSD, Bayer, Viatris, Tarian
Travel, Accommodations, Expenses: MSD, Pierre Fabre
Brice Chanez
Employment: Bristol Myers Squibb, AstraZeneca, Servier, Viatris
Leadership: Servier
Honoraria: Bristol Myers Squibb, Servier, Amgen (Inst), AstraZeneca/MedImmune (Inst)
Travel, Accommodations, Expenses: Amgen, Pfizer, Bristol Myers Squibb, Servier
No other potential conflicts of interest were reported.
See accompanying Editorial, p. 547
DISCLAIMER
The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of their affiliated institutions.
PRIOR PRESENTATION
Presented in part as an online abstract at the 2024 ASCO Annual Meeting, Chicago, IL, May 31-June 4, 2024 (J Clin Oncol. 2024; 42 [suppl 16]:e16305).
SUPPORT
Supported by the GIRCI ValoData 2019 grant.
DATA SHARING STATEMENT
The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
AUTHOR CONTRIBUTIONS
Conception and design: Berenice Collineau, Brice Chanez
Provision of study materials or patients: Cecile Bannier-Braticevic, Elika Loir, Franck Espinosa, Christelle de la Fouchardière
Collection and assembly of data: Berenice Collineau, Cecile Bannier-Braticevic, Elika Loir, Louis Tassy, Franck Espinosa, Christophe Manceau, Brice Chanez
Data analysis and interpretation: Berenice Collineau, Julia Gilhodes, Céline Delaunay, Philippe Rochigneux, Damien Bruyat, Christophe Manceau, Christelle de la Fouchardière, Emmanuel Mitry, Brice Chanez
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Factors Associated With Toxicity of FOLFIRINOX in Elderly Patients With Pancreatic Ductal Adenocarcinoma
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Céline Delaunay
Honoraria: Pierre Fabre
Travel, Accommodations, Expenses: Fresenius Kabi
Philippe Rochigneux
Honoraria: AstraZeneca, Novartis (Inst), Bristol Myers Squibb Foundation (Inst), Viatris, Roche
Research Funding: Novartis (Inst), AstraZeneca (Inst)
Travel, Accommodations, Expenses: Pfizer, Roche
Christelle de la Fouchardière
Consulting or Advisory Role: Bristol Myers Squibb, Amgen, Servier, Pierre Fabre, MSD Oncology, Roche/Genentech, Daichi-Sankyo, Astellas Pharma, Gilead Sciences, BeiGene, Jazz Pharmaceuticals, Takeda, AbbVie, AstraZeneca
Research Funding: Pierre Fabre (Inst), Servier (Inst), MSD (Inst), Agenus (Inst)
Travel, Accommodations, Expenses: Pierre Fabre, Servier, MSD Oncology, Amgen, AstraZeneca
Emmanuel Mitry
Honoraria: Pierre Fabre, AstraZeneca/Daiichi Sankyo, Servier, Esteve, MSD, Bayer, Viatris, Tarian
Travel, Accommodations, Expenses: MSD, Pierre Fabre
Brice Chanez
Employment: Bristol Myers Squibb, AstraZeneca, Servier, Viatris
Leadership: Servier
Honoraria: Bristol Myers Squibb, Servier, Amgen (Inst), AstraZeneca/MedImmune (Inst)
Travel, Accommodations, Expenses: Amgen, Pfizer, Bristol Myers Squibb, Servier
No other potential conflicts of interest were reported.
REFERENCES
- 1.Klein AP: Pancreatic cancer epidemiology: Understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 18:493-502, 2021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Rahib L, Wehner MR, Matrisian LM, et al. : Estimated projection of US cancer incidence and death to 2040. JAMA Netw Open 4:e214708, 2021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kenis C, Decoster L, Bastin J, et al. : Functional decline in older patients with cancer receiving chemotherapy: A multicenter prospective study. J Geriatr Oncol 8:196-205, 2017 [DOI] [PubMed] [Google Scholar]
- 4.Hutchins LF, Unger JM, Crowley JJ, et al. : Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061-2067, 1999 [DOI] [PubMed] [Google Scholar]
- 5.Soubeyran P, Bellera C, Goyard J, et al. : Screening for vulnerability in older cancer patients: The ONCODAGE prospective multicenter cohort study. PLoS One 9:e115060, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Decoster L, Van Puyvelde K, Mohile S, et al. : Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: An update on SIOG recommendations. Ann Oncol 26:288-300, 2015 [DOI] [PubMed] [Google Scholar]
- 7.Jolly TA, Deal AM, Nyrop KA, et al. : Geriatric assessment-identified deficits in older cancer patients with normal performance status. Oncologist 20:379-385, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Mohile SG, Dale W, Somerfield MR, et al. : Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol 36:2326-2347, 2018 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Wildiers H, Heeren P, Puts M, et al. : International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 32:2595-2603, 2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Conroy T, Desseigne F, Ychou M, et al. : FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817-1825, 2011 [DOI] [PubMed] [Google Scholar]
- 11.Fietkau R, Ghadimi M, Grützmann R, et al. : Randomized phase III trial of induction chemotherapy followed by chemoradiotherapy or chemotherapy alone for nonresectable locally advanced pancreatic cancer: First results of the CONKO-007 trial. J Precious Oncol 40:4008, 2022 [Google Scholar]
- 12.Conroy T, Hammel P, Hebbar M, et al. : FOLFIRINOX or Gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379:2395-2406, 2018 [DOI] [PubMed] [Google Scholar]
- 13.Conroy T, Castan F, Lopez A, et al. : Five-year outcomes of FOLFIRINOX vs gemcitabine as adjuvant therapy for pancreatic cancer: A randomized clinical trial. JAMA Oncol 8:1571-1578, 2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Janssen QP, Buettner S, Suker M, et al. : Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis. J Natl Cancer Inst 111:782-794, 2019 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Von Hoff DD, Ervin T, Arena FP, et al. : Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691-1703, 2013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Nichetti F, Rota S, Ambrosini P, et al. : NALIRIFOX, FOLFIRINOX, and gemcitabine with nab-paclitaxel as first-line chemotherapy for metastatic pancreatic cancer: A systematic review and meta-analysis. JAMA Netw Open 7:e2350756, 2024 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Dotan E, Catalano PJ, Lenchik L, et al. : A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer (GIANT): ECOG-ACRIN EA2186. J Precious Oncol 42:4003, 2024 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Wang-Gillam A, Li CP, Bodoky G, et al. : Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial. Lancet 387:545-557, 2016 [DOI] [PubMed] [Google Scholar]
- 19.Wainberg ZA, Melisi D, Macarulla T, et al. : NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): A randomised, open-label, phase 3 trial. Lancet 402:1272-1281, 2023 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, et al. : Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: Results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 31:23-29, 2013 [DOI] [PubMed] [Google Scholar]
- 21.Mizrahi JD, Rogers JE, Hess KR, et al. : Modified FOLFIRINOX in pancreatic cancer patients age 75 or older. Pancreatology 20:501-504, 2020 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Weniger M, Moir J, Damm M, et al. : Neoadjuvant therapy in elderly patients receiving FOLFIRINOX or gemcitabine/nab-paclitaxel for borderline resectable or locally advanced pancreatic cancer is feasible and lead to a similar oncological outcome compared to non-aged patients—Results of the RESPECT-Study. Surg Oncol 35:285-297, 2020 [DOI] [PubMed] [Google Scholar]
- 23.Han SY, Kim DU, Seol YM, et al. : First-line chemotherapy in very elderly patients with metastatic pancreatic cancer: Gemcitabine monotherapy vs combination chemotherapy. World J Clin Cases 8:4022-4033, 2020 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Guion-Dusserre J-F, Bertaut A, Ghiringhelli F, et al. : Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy. World J Gastroenterol 22:9378-9386, 2016 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Domagała-Haduch M, Robek A, Wnuk J, et al. : Analysis of the efficacy and tolerability of FOLFIRINOX chemotherapy treatment in patients over 65 years of age with diagnosis of advanced adenocarcinoma of the pancreas. Contemp Oncol (Pozn) 27:10-13, 2023 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Li X, Huang D-B, Zhang Q, et al. : The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer. Pancreatology 20:95-100, 2020 [DOI] [PubMed] [Google Scholar]
- 27.Haute Autorité de Santé, & Fédération Française de Nutrition : Diagnostic de la dénutrition chez la personne de 70 ans et plus [Good practice recommendations]. Haute Autorité de Santé. 2021 [Google Scholar]
- 28.Jeong HT, Kim HG, Han J: Efficacy and toxicity of palliative chemotherapy in elderly patients with advanced pancreatic cancer. Pancreas 53:e268-e273, 2024 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Macarulla Mercade T, Pazo Cid R, Womack M, et al. : 323P NALIRIFOX versus nab-paclitaxel and gemcitabine (Gem+NabP) in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Subgroup analysis of patients aged 65 years or older in NAPOLI 3. Ann Oncol 35:S135-S136, 2024 [Google Scholar]
- 30.Buzyn A: Les apports des Plans cancer à la cancérologie. Oncologie 16:4-6, 2014 [Google Scholar]
- 31.Bullock AF, Greenley SL, McKenzie GAG, et al. : Relationship between markers of malnutrition and clinical outcomes in older adults with cancer: Systematic review, narrative synthesis and meta-analysis. Eur J Clin Nutr 74:1519-1535, 2020 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Takeda T, Sasaki T, Suzumori C, et al. : The impact of cachexia and sarcopenia in elderly pancreatic cancer patients receiving palliative chemotherapy. Int J Clin Oncol 26:1293-1303, 2021 [DOI] [PubMed] [Google Scholar]
- 33.Cruz-Jentoft AJ, Bahat G, Bauer J, et al. : Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing 48:601-631, 2019 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Assenat E, Ben Abdelghani M, Gourgou S, et al. : 507O impact of lean body mass-based oxaliplatin dosage on neurotoxicity in adjuvant treatment of stage III colorectal cancer: Final results of the phase II randomized multicenter LEANOX trial. Ann Oncol 35:S431, 2024 [Google Scholar]
- 35.Baldini C, Escande A, Bouché O, et al. : Safety and efficacy of FOLFIRINOX in elderly patients with metastatic or locally advanced pancreatic adenocarcinoma: A retrospective analysis. Pancreatology 17:146-149, 2017 [DOI] [PubMed] [Google Scholar]
- 36.Feliu J, Espinosa E, Basterretxea L, et al. : Prediction of unplanned hospitalizations in older patients treated with chemotherapy. Cancers (Basel) 13:1437, 2021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Gill TM, Gahbauer EA, Han L, et al. : The role of intervening hospital admissions on trajectories of disability in the last year of life: Prospective cohort study of older people. BMJ 350:h2361, 2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Gill TM, Allore HG, Gahbauer EA, et al. : Change in disability after hospitalization or restricted activity in older persons. JAMA 304:1919-1928, 2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Johns AC, Yang M, Wei L, et al. : Risk factors for immune checkpoint inhibitor immunotherapy toxicity among older adults with cancer. Oncologist 28:e625-e632, 2023 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Mohile SG, Mohamed MR, Xu H, et al. : Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): A cluster-randomised study. Lancet 398:1894-1904, 2021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Bascoul-Mollevi C, Gourgou S, Borg C, et al. : Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER PRODIGE 23): Health-related quality of life longitudinal analysis. Eur J Cancer 186:151-165, 2023 [DOI] [PubMed] [Google Scholar]
- 42.Katz MHG, Shi Q, Meyers J, et al. : Efficacy of preoperative mFOLFIRINOX vs mFOLFIRINOX plus hypofractionated radiotherapy for borderline resectable adenocarcinoma of the pancreas: The A021501 phase 2 randomized clinical trial. JAMA Oncol 8:1263-1270, 2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.