Annals of Surgical Oncology

, Volume 20, Issue 12, pp 3787–3793

Phase II Study of Induction Fixed-Dose Rate Gemcitabine and Bevacizumab Followed by 30 Gy Radiotherapy as Preoperative Treatment for Potentially Resectable Pancreatic Adenocarcinoma

  • George Van BurenII
  • Ramesh K. Ramanathan
  • Alyssa M. Krasinskas
  • Ryan P. Smith
  • Gerard J. Abood
  • Nathan Bahary
  • Barry C. Lembersky
  • Yongli Shuai
  • Douglas M. Potter
  • David L Bartlett
  • Amer H. Zureikat
  • Herbert J. Zeh
  • A. James Moser
Pancreatic Tumors

DOI: 10.1245/s10434-013-3161-9

Cite this article as:
Van Buren, G., Ramanathan, R.K., Krasinskas, A.M. et al. Ann Surg Oncol (2013) 20: 3787. doi:10.1245/s10434-013-3161-9

Abstract

Background

Eighty percent of patients with resected pancreatic ductal carcinoma (PDC) experience treatment failure within 2 years. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with the angiogenesis inhibitor bevacizumab (BEV) and accelerated 30 Gy radiotherapy (RT) would improve outcomes among patients with potentially resectable PDC.

Methods

This phase II trial tested induction FDR GEM (1,500 mg/m2) plus BEV (10 mg/kg IV) every 2 weeks for three cycles followed by accelerated RT (30 Gy in 10 fractions) plus BEV directed at gross tumor volume plus a 1–2 cm vascular margin. Subjects underwent laparoscopy and resection after day 85. Therapy was considered effective if the complete pathologic response rate exceeded 10 % and the margin-negative resection rate exceeded 80 %.

Results

Fifty-nine subjects were enrolled; 29 had potential portal vein involvement. Two grade 4 (3.4 %) and 19 grade 3 toxicities (32.8 %) occurred. Four subjects manifested radiographic progression, and 10 had undetected carcinomatosis. Forty-three pancreatic resections (73 %) were performed, including 19 portal vein resections (44 %). Margin-negative outcomes were observed in 38 (88 %, 95 % confidence interval [CI] 75–96), with one complete pathologic response (2.3 %; 95 % CI 0.1–12). There were seven (6 grade 3; 1 grade 4) wound complications (13 %). Median overall survival for the entire cohort was 16.8 months (95 % CI 14.9–21.3) and 19.7 months (95 % CI 16.5–28.2) after resection.

Conclusions

Induction therapy with FDR GEM and BEV, followed by accelerated BEV/RT to 30 Gy, was well tolerated. Although both effectiveness criteria were achieved, survival outcomes were equivalent to published regimens.

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • George Van BurenII
    • 1
  • Ramesh K. Ramanathan
    • 7
  • Alyssa M. Krasinskas
    • 2
  • Ryan P. Smith
    • 3
  • Gerard J. Abood
    • 1
  • Nathan Bahary
    • 4
  • Barry C. Lembersky
    • 4
  • Yongli Shuai
    • 5
  • Douglas M. Potter
    • 5
    • 6
  • David L Bartlett
    • 1
  • Amer H. Zureikat
    • 1
  • Herbert J. Zeh
    • 1
    • 9
  • A. James Moser
    • 1
    • 8
  1. 1.Division of Surgical OncologyUPMC Pancreatic Cancer CenterPittsburghUSA
  2. 2.Department of PathologyUPMC Pancreatic Cancer CenterPittsburghUSA
  3. 3.Department of Radiation OncologyUPMC Pancreatic Cancer CenterPittsburghUSA
  4. 4.Department of Medical OncologyUPMC Pancreatic Cancer CenterPittsburghUSA
  5. 5.The University of Pittsburgh Cancer Institute Biostatistics FacilityPittsburghUSA
  6. 6.Biostatistics Department, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  7. 7.Translational Genomics Research InstituteScottsdaleUSA
  8. 8.Institute for Hepatobiliary and Pancreatic SurgeryBeth Israel Deaconess Medical CenterBostonUSA
  9. 9.Division of Gastrointestinal Surgical OncologyUPMC Cancer PavilionPittsburghUSA