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

Nguyen H. Tran, Vaibhav Sahai, Kent A. Griffith, Hari Nathan, Ravi Kaza, Kyle C. Cuneo, Jiaqi Shi, Edward Kim, Christopher J. Sonnenday, Clifford S. Cho, Theodore S. Lawrence, Mark M. Zalupski

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)124-133
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume106
Issue number1
DOIs
StatePublished - Jan 1 2020

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gemcitabine
Pancreatic Neoplasms
radiation therapy
Radiotherapy
cancer
dosage
confidence
intervals
progressions
Confidence Intervals
Disease-Free Survival
therapy
Survival
vomiting
nausea
Neoadjuvant Therapy
Therapeutics
Neutropenia
toxicity
organs

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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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.; Sahai, Vaibhav; Griffith, Kent A.; Nathan, Hari; Kaza, Ravi; Cuneo, Kyle C.; Shi, Jiaqi; Kim, Edward; Sonnenday, Christopher J.; Cho, Clifford S.; Lawrence, Theodore S.; Zalupski, Mark M.

In: International Journal of Radiation Oncology Biology Physics, Vol. 106, No. 1, 01.01.2020, p. 124-133.

Research output: Contribution to journalArticle

Tran, Nguyen H. ; Sahai, Vaibhav ; Griffith, Kent A. ; Nathan, Hari ; Kaza, Ravi ; Cuneo, Kyle C. ; Shi, Jiaqi ; Kim, Edward ; Sonnenday, Christopher J. ; Cho, Clifford S. ; Lawrence, Theodore S. ; Zalupski, Mark M. / Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer. In: International Journal of Radiation Oncology Biology Physics. 2020 ; Vol. 106, No. 1. pp. 124-133.
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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.",
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T1 - Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer

AU - Tran, Nguyen H.

AU - Sahai, Vaibhav

AU - Griffith, Kent A.

AU - Nathan, Hari

AU - Kaza, Ravi

AU - Cuneo, Kyle C.

AU - Shi, Jiaqi

AU - Kim, Edward

AU - Sonnenday, Christopher J.

AU - Cho, Clifford S.

AU - Lawrence, Theodore S.

AU - Zalupski, Mark M.

PY - 2020/1/1

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N2 - 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.

AB - 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.

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