TY - JOUR
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.
N1 - Funding Information:
M.M.Z. reports grants from Halozyme, grants from Oncomed, grants from Merck , and grants from Medimmune, outside the submitted work.
Funding Information:
We thank the patients and their families for their participation in the study. We would also like to acknowledge all the investigators and research staff for enrolling their patients on this trial. This trial was supported by the University of Michigan Rogel Cancer Center and the National Cancer Institute of the National Institutes of Health under award number P30CA046592 and K08CA234222 (JS).
Funding Information:
M.M.Z. reports grants from Halozyme, grants from Oncomed, grants from Merck, and grants from Medimmune, outside the submitted work.Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA046592 and K08CA234222 (JS).We thank the patients and their families for their participation in the study. We would also like to acknowledge all the investigators and research staff for enrolling their patients on this trial. This trial was supported by the University of Michigan Rogel Cancer Center and the National Cancer Institute of the National Institutes of Health under award number P30CA046592 and K08CA234222 (JS). Disclosures: E.K. reports personal fees from Armo, personal fees from Vicus, personal fees from Guardant Health, grants from BMS, grants from Astellas, grants from Samumed, grants from Boston Biomedical, grants from Halozyme, grants from EpicentRx, grants from Merck, grants from Oncomed, and grants from Celgene, outside the submitted work. V.S. reports institutional grants from Celgene, Incyte, Bristol-Myers Squibb, Agios, Clovis, Halozyme, Merck, and MedImmune. He has also served in the role of a consultant for NewLink Genetics, Incyte, Celgene, and Halozyme.
Funding Information:
Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA046592 and K08CA234222 (JS).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/1/1
Y1 - 2020/1/1
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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U2 - 10.1016/j.ijrobp.2019.08.057
DO - 10.1016/j.ijrobp.2019.08.057
M3 - Article
C2 - 31494181
AN - SCOPUS:85076032662
SN - 0360-3016
VL - 106
SP - 124
EP - 133
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -