Dataset Information

Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer.

ABSTRACT:

Purpose

Preoperative therapy in borderline resectable pancreatic cancer (BRPC) is intended to increase R0 resection rates. An optimal approach in BRPC is yet to be defined.

Methods and materials

Patients with BRPC, confirmed adenocarcinoma, performance status ?1, and adequate organ function enrolled in a single-institution, phase 2 trial. Patients received FOLFIRINOX × 6 cycles, then radiation therapy (50 Gy in 25 fractions) concurrent with fixed-dose rate gemcitabine (1 g/m² over 100 minutes) followed by 2 additional gemcitabine infusions. Computed tomography scans were performed at 2-month intervals during treatment. Patients without distant disease were offered surgical exploration. The primary objective was R0 resection rate with an alternate hypothesis of 55%. Secondary objectives included median progression-free survival (PFS), median overall survival (OS), response rate, and safety. The trial registration number is NCT01661088.

Results

Twenty-five patients with median age of 60 years (range, 47-77 years) enrolled from November 2011 through January 2017. Twenty-one (84%) completed FOLFIRINOX and 19 (76%) completed all protocol therapy. Treatment-related grade 3 to 4 toxicities included neutropenia (40%), nausea and vomiting (28%), diarrhea (16%), and fatigue (12%). Eighteen patients (72%) underwent laparotomy, 13 (52%) were resected (all R0). The median PFS and OS in 25 patients were 13.1 months (95% confidence interval [CI], 7.3-24.7) and 24.4 months (95% CI, 12.6-40.0), respectively. For resected patients, median PFS was 21.6 months (95% CI, 8.2-37.1) and OS was 37.1 months (95% CI, 15.4-not reached).

Conclusions

Neoadjuvant therapy with FOLFIRINOX, followed by intensity modulated radiation therapy concurrent with fixed-dose-rate gemcitabine in BRPC is feasible and tolerated. Although the alternate hypothesis was not met, the OS of the resected cohort was favorable.

SUBMITTER: Tran NH

PROVIDER: S-EPMC7245020 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer.

Tran Nguyen H NH Sahai Vaibhav V Griffith Kent A KA Nathan Hari H Kaza Ravi R Cuneo Kyle C KC Shi Jiaqi J Kim Edward E Sonnenday Christopher J CJ Cho Clifford S CS Lawrence Theodore S TS Zalupski Mark M MM

International journal of radiation oncology, biology, physics 20190905 1

<h4>Purpose</h4>Preoperative therapy in borderline resectable pancreatic cancer (BRPC) is intended to increase R0 resection rates. An optimal approach in BRPC is yet to be defined.<h4>Methods and materials</h4>Patients with BRPC, confirmed adenocarcinoma, performance status ≤1, and adequate organ function enrolled in a single-institution, phase 2 trial. Patients received FOLFIRINOX × 6 cycles, then radiation therapy (50 Gy in 25 fractions) concurrent with fixed-dose rate gemcitabine (1 g/m<sup>2 ...[more]

PMID: 31494181

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Project description:BackgroundNeoadjuvant chemoradiotherapy can provide downstaging and improve margin negativity for borderline resectable and resectable pancreatic adenocarcinoma [(B)RPC]. Little is known about the relative efficacy of capecitabine (CAPE)-based vs. gemcitabine (GEM)-based 3-week chemoradiation (3WCRT) with 36 Gy in 15 fractions. This study aimed to compare the odds of achieving surgical resection, time to progression (TTP), and overall survival (OS) of patients treated with 3WCRT with concurrent CAPE versus GEM.MethodsA retrospective cohort study was conducted, examining medical records from a single center for patients with (B)RPC treated with 3WCRT between 1/2009-12/2020. Odd ratios (OR) of achieving surgical resection were estimated using logistic regression for univariable and multivariable analyses. Median TTP (mTTP) and median OS (mOS) were estimated using the Kaplan-Meier method. Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) of progression and survival in univariable and multivariable analyses.ResultsThirty-one patients were included in the analysis. Twenty-two (71%) patients were treated with CAPE, while 9 (29%) were treated with GEM. All patients in the GEM group were borderline resectable, vs. 18 (82%) patients in the CAPE group, P=0.30. Nineteen (86%) patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, vs. 4 (44%) patients in the GEM group, P=0.03. The CAPE group had higher odds of achieving surgical resection [OR =9.33; 95% confidence interval (CI): 1.50-58.20]. Adjusting for covariates, the odds of achieving surgical resection were still statistically higher in the CAPE group vs. the GEM group (OR =25.34; 95% CI: 1.14-563.72). The CAPE group had superior mTTP compared to the GEM group (15.4 months, 95% CI: 4.9-71.1 vs. 4.0 months, 95% CI: 0.4-14.5; P=0.01), corresponding to a hazard ratio of 0.33 (95% CI: 0.14-0.81). Adjusting for covariates this effect persisted; the adjusted hazard ratio (AHR) for progression was 0.24 (95% CI: 0.08-0.77). Cox proportional hazards analysis also demonstrated that the CAPE group had superior OS compared to the GEM group in unadjusted (HR =0.13; 95% CI: 0.04-0.40) and adjusted models (HR =0.13, 95% CI: 0.03-0.52).ConclusionsFor neoadjuvant 3WCRT, this hypothesis-generating study suggests concurrent CAPE may be a more effective radiosensitizer than GEM for patients with (B)RPC.

Project description:BackgroundFOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.MethodsWe performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.ResultsWe included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.ConclusionsThis patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

Project description:Background The complete resection rate of pancreatic cancer has increased because of the advent of efficacious first-line treatments for unresectable pancreatic cancer. Still, strategies regarding adjuvant therapy after neoadjuvant FOLFIRINOX treatment remain to be established. Methods Data on 144 patients with borderline resectable and locally advanced pancreatic cancer who underwent resection after neoadjuvant FOLFIRINOX between January 2013 and April 2021 were retrospectively reviewed. Results Among the study patients, 113 patients (78.5%) were diagnosed with borderline resectable pancreatic cancer and 31 patients (21.5%) were diagnosed with locally advanced pancreatic cancer. Seventy-five patients (52.1%) received radiotherapy before surgery. After radical resection, 84 patients (58.3%) received 5-fluorouracil-based adjuvant therapy and 60 patients (41.7%) received non-5-fluorouracil-based adjuvant therapy. Adjuvant therapy with 5-fluorouracil-based regimen [hazard ratio (HR), 0.43 (95% CI, 0.21–0.87); p = 0.019], preoperative assessment as locally advanced pancreatic cancer [HR, 2.87 (95% CI, 1.08–7.64); p = 0.035], positive resection margin [HR, 3.91 (95% CI, 1.71–8.94); p = 0.001], and presence of pathologic lymph node involvement [HR, 2.31 (95% CI, 1.00–5.33), p = 0.050] were associated with decreased recurrence-free survival. Adjuvant therapy with 5-fluorouracil-based regimen [HR, 0.35 (95% CI, 0.15–0.84); p = 0.018], positive resection margin [HR, 4.14 (95% CI, 1.75–9.78); p = 0.001], presence of pathologic lymph node involvement [HR, 3.36 (95% CI, 1.23–9.15); p = 0.018], poor differentiation [HR, 5.69 (95% CI, 1.76–18.36); p = 0.004], and dose reduction during adjuvant therapy [HR, 1.78 (95% CI, 1.24–24.37); p = 0.025] were associated with decreased overall survival. Conclusions The 5-fluorouracil-based adjuvant therapy seems to be the proper adjuvant therapy for patients who received neoadjuvant FOLFIRINOX for borderline resectable and locally advanced pancreatic cancer.

Dataset Information

Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer.

Purpose

Methods and materials

Results

Conclusions

Publications

Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer.

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