Chi Lin1, Vivek Verma2, Quan P Ly3, Audrey Lazenby4, Aaron Sasson5, James K Schwarz6, Jane L Meza7, Chandrakanth Are3, Sicong Li8, Shuo Wang8, Stephen M Hahn9, Jean L Grem6. 1. Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, USA. Electronic address: clin@unmc.edu. 2. Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, USA. 3. Department of Surgery, University of Nebraska Medical Center, Omaha, USA. 4. Department of Pathology, University of Nebraska Medical Center, Omaha, USA. 5. Department of Surgery, Stony Brook School of Medicine, Stony Brook, USA. 6. Department of Internal Medicine, Division of Hematology Oncology, University of Nebraska Medical Center, Omaha, USA. 7. Department of Biostatistics, University of Nebraska Medical Center, Omaha, USA. 8. Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, USA. 9. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Abstract
INTRODUCTION: The HIV protease inhibitor nelfinavir (NFV) displays notable radiosensitizing effects. There have been no studies evaluating combined stereotactic body radiotherapy (SBRT) and NFV for borderline/unresectable pancreatic cancer. The primary objective of this phase I trial (NCT01068327) was to determine the maximum tolerated SBRT/NFV dose, and secondarily evaluate outcomes. METHODS: Following initial imaging, pathologic confirmation, and staging laparoscopy, subjects initially received three 3-week cycles of gemcitabine/leucovorin/fluorouracil; patients without radiologic progression received 5-fraction SBRT/NFV. Dose escalation was as follows: (1) 25 Gy/625 mg BID ×3wks; (2) 25 Gy/1250 mg BID ×3wks; (3) 30 Gy/1250 mg BID ×3wks; (4) 35 Gy/1250 mg BID ×3wks; (5) 35 Gy/1250 mg BID ×5wks; and (6) 40 Gy/1250 mg BID ×5wks. Pancreaticoduodenectomy was performed thereafter if resectable; if not, gemcitabine/leucovorin/fluorouracil was administered. RESULTS: Forty-six patients enrolled (10/2008-5/2013); 39 received protocol-directed therapy. Sixteen (41%) experienced any grade ≥2 event during and 1 month after SBRT. Four grade 3 and both grade 4 events occurred in a single patient at the initial dose level. 40 Gy/1250 mg BID ×5wks was the maximum tolerated dose. Five patients had late gastrointestinal bleeding (n = 2 superior mesenteric artery pseudo-aneurysm, n = 1 disease progression, n = 1 lower GI tract, n = 1 unknown location). The median overall survival was 14.4 months. Six (15%) patients recurred locally; median local failure-free survival was not reached. The median distant failure-free survival was 11 months, and median all failure-free survival was 10 months. CONCLUSIONS: Concurrent SBRT (40 Gy)/NFV (1250 mg BID) for locally advanced pancreatic cancer is feasible and safe, although careful attention to treatment planning parameters is recommended to reduce the incidence of late gastrointestinal bleeding. Published by Elsevier B.V.
INTRODUCTION: The HIV protease inhibitor nelfinavir (NFV) displays notable radiosensitizing effects. There have been no studies evaluating combined stereotactic body radiotherapy (SBRT) and NFV for borderline/unresectable pancreatic cancer. The primary objective of this phase I trial (NCT01068327) was to determine the maximum tolerated SBRT/NFV dose, and secondarily evaluate outcomes. METHODS: Following initial imaging, pathologic confirmation, and staging laparoscopy, subjects initially received three 3-week cycles of gemcitabine/leucovorin/fluorouracil; patients without radiologic progression received 5-fraction SBRT/NFV. Dose escalation was as follows: (1) 25 Gy/625 mg BID ×3wks; (2) 25 Gy/1250 mg BID ×3wks; (3) 30 Gy/1250 mg BID ×3wks; (4) 35 Gy/1250 mg BID ×3wks; (5) 35 Gy/1250 mg BID ×5wks; and (6) 40 Gy/1250 mg BID ×5wks. Pancreaticoduodenectomy was performed thereafter if resectable; if not, gemcitabine/leucovorin/fluorouracil was administered. RESULTS: Forty-six patients enrolled (10/2008-5/2013); 39 received protocol-directed therapy. Sixteen (41%) experienced any grade ≥2 event during and 1 month after SBRT. Four grade 3 and both grade 4 events occurred in a single patient at the initial dose level. 40 Gy/1250 mg BID ×5wks was the maximum tolerated dose. Five patients had late gastrointestinal bleeding (n = 2 superior mesenteric artery pseudo-aneurysm, n = 1 disease progression, n = 1 lower GI tract, n = 1 unknown location). The median overall survival was 14.4 months. Six (15%) patients recurred locally; median local failure-free survival was not reached. The median distant failure-free survival was 11 months, and median all failure-free survival was 10 months. CONCLUSIONS: Concurrent SBRT (40 Gy)/NFV (1250 mg BID) for locally advanced pancreatic cancer is feasible and safe, although careful attention to treatment planning parameters is recommended to reduce the incidence of late gastrointestinal bleeding. Published by Elsevier B.V.
Entities:
Keywords:
Nelfinavir; Pancreas; Pancreatic cancer; Stereotactic body radiation therapy
Authors: Chi Lin; Vivek Verma; Audrey Lazenby; Quan P Ly; Lyudmyla D Berim; James K Schwarz; Madi Madiyalakan; Christopher F Nicodemus; Michael A Hollingsworth; Jane L Meza; Chandrakanth Are; James Padussis; Jean L Grem Journal: Am J Clin Oncol Date: 2019-10 Impact factor: 2.339
Authors: Kyung Hwan Kim; Han Sang Kim; Sang Cheol Kim; DooA Kim; Yong Bae Kim; Hyun Cheol Chung; Sun Young Rha Journal: Front Oncol Date: 2020-09-11 Impact factor: 6.244
Authors: Eugene J Koay; Alexander N Hanania; William A Hall; Cullen M Taniguchi; Neal Rebueno; Sten Myrehaug; Katharine L Aitken; Laura A Dawson; Christopher H Crane; Joseph M Herman; Beth Erickson Journal: Pract Radiat Oncol Date: 2020-02-13