SS 38 - GI 4 - Hepato-Pancreatic-Biliary
278 - Phase I Trial of Concurrent Stereotactic Body Radiation Therapy and Nelfinavir for Locally Advanced Borderline or Unresectable Pancreatic Cancer-Final Results
Wednesday, October 24
11:30 AM - 11:40 AM
Location: Room 206
Chi Lin, MD, PhD, MS
University of Nebraska Medical Center: Associate Professor: Employee
DHHS/NIH/NCI: Focus is on translational studies that address basic and clinical issues of importance to improving outcome of patients with pancreatic cancer. Role: Project Leader Title of the project: Novel Target(s) in the Radiosensitization of Pancreatic Cancer, Research Grants; Eppley Cancer center at UNMC: Research Grants, To purchase a research drug
ASCO 2018 annual meeting: Colorectal track leader; University of Nebraska Medical Center,: Vice chair of Research
Phase I Trial of Concurrent Stereotactic Body Radiation Therapy and Nelfinavir for Locally Advanced Borderline or Unresectable Pancreatic Cancer-Final Results
C. Lin1, V. Verma1, Q. Ly2, J. Schwarz2, J. Meza2, A. Sasson3, C. Are2, B. Kos2, and J. Grem2; 1Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, 2University of Nebraska Medical Center, Omaha, NE, 3Stony Brook School of Medicine, Stony, NY
Purpose/Objective(s): The HIV protease inhibitor nelfinavir (NFV) displays notable radiosensitizing effects. There have been no studies evaluating combined stereotactic body radiation therapy (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.
Materials/Methods: Following initial imaging, pathologic confirmation, and staging laparoscopy, subjects initially received 3 3-week cycles of gemcitabine/leucovorin/fluorouracil; patients without radiologic progression received SBRT(5 fractions)/NFV. Dose escalation was as follows: 1) 25 Gy/625 mg BID x 3 wk; 2) 25 Gy/1250 mg BID x 3 wk; 3)30 Gy/1250 mg BID x 3 wk; 4) 35 Gy/1250 mg BID x 3 wk; 5) 35 Gy/1250 mg BID x 5wk; and 6) 40 Gy/1250 mg BID x 5 wk. Pancreaticoduodenectomy was performed thereafter if deemed resectable; if not, gemcitabine/leucovorin/fluorouracil was administered.
Results: Forty-six patients enrolled (10/2008-5/2013). Thirty-nine patients received SBRT/NFV on protocol; 16 (41%) experienced any grade ≥2 adverse event (AEs) during and 1 month after SBRT. There were 21, 11, and 2 instances of grades 2, 3, and 4 toxicities, respectively. Four instances of grade 3 events & both grade 4 events occurred in a single patient (started prior to SBRT/NFV) at the initial dose level. The final dose level was the maximum tolerated dose. Long-term follow up revealed that 5 patients had late gastrointestinal (GI) bleed (2, superior mesenteric artery pseudoaneusysm; 1, unknown; 1, negative esophagogastroduodenoscopy; 1, disease progression invading GI). The median overall survival was 14.4 months. Six (15%) patients experienced a local failure; the median local failure-free survival was not reached. Twenty-six had a distant failure as the first failure site (9, liver; 6, lung; 9, peritoneum). The median distant failure-free survival was 11 months, and the median all failure-free survival was 10 months. Twelve patients underwent pancreaticoduodenectomy; their median survival (19 months) was similar to those of unresected patients receiving 35-40 Gy (18 months) (p=0.924). As compared to those receiving 25-30 Gy (10 months), there was a trend towards higher survival in whom 35-40 Gy was delivered (p=0.083).
Conclusion: Concurrent SBRT (40 Gy)/NFV (1250 mg BID) for locally-advanced pancreatic cancer is safe and yields encouraging outcomes; a phase II study is currently ongoing. A close attention to SBRT plan & delivery is warranted to decrease the risk of late GI bleed.
Author Disclosure: C. Lin: Research Grant; Eppley Cancer center at UNMC, DHHS/NIH/NCI. To purchase a research drug; Eppley Cancer center at UNMC. Focus is on translational studies that address basic and clinical issues of importance to improving outcome of patients with pancreatic cancer. Role: Project Leader Title of the project: Novel Target(s) in the Radiosensitization of Pancreatic Cancer; DHHS/NIH/NCI. Vice chair of Research; University of Nebraska Medical Center. Colorectal track leader; ASCO 2018 annual meeting. V. Verma: None. Q. Ly: None. J. Schwarz: None. J. Meza: None. A. Sasson: None. C. Are: None.