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

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

Supported in part by a research grant from Genentech to AJM, AK, and DMP. Genentech had no control over trial design, data acquisition and analysis, or document preparation. Special thanks to Jennifer Steve at the University of Pittsburgh Department of Surgery for data acquisition and analysis.

Disclosure

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Division of Surgical Oncology, UPMC Pancreatic Cancer Center, Pittsburgh, PA, USA

    George Van Buren II MD, Gerard J. Abood MD, David L Bartlett MD, Amer H. Zureikat MD, Herbert J. Zeh MD & A. James Moser MD

  2. Department of Pathology, UPMC Pancreatic Cancer Center, Pittsburgh, PA, USA

    Alyssa M. Krasinskas MD

  3. Department of Radiation Oncology, UPMC Pancreatic Cancer Center, Pittsburgh, PA, USA

    Ryan P. Smith MD

  4. Department of Medical Oncology, UPMC Pancreatic Cancer Center, Pittsburgh, PA, USA

    Nathan Bahary MD & Barry C. Lembersky MD

  5. The University of Pittsburgh Cancer Institute Biostatistics Facility, Pittsburgh, PA, USA

    Yongli Shuai PhD & Douglas M. Potter PhD

  6. Biostatistics Department, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Douglas M. Potter PhD

  7. Translational Genomics Research Institute, Scottsdale, AZ, USA

    Ramesh K. Ramanathan MD

  8. Institute for Hepatobiliary and Pancreatic Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    A. James Moser MD

  9. Division of Gastrointestinal Surgical Oncology, UPMC Cancer Pavilion, Pittsburgh, PA, USA

    Herbert J. Zeh MD

Authors
  1. George Van Buren II MD
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  10. David L Bartlett MD
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  11. Amer H. Zureikat MD
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Corresponding authors

Correspondence to Herbert J. Zeh MD or A. James Moser MD.

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Van Buren, G., Ramanathan, R.K., Krasinskas, A.M. et al. Phase II Study of Induction Fixed-Dose Rate Gemcitabine and Bevacizumab Followed by 30 Gy Radiotherapy as Preoperative Treatment for Potentially Resectable Pancreatic Adenocarcinoma. Ann Surg Oncol 20, 3787–3793 (2013). https://doi.org/10.1245/s10434-013-3161-9

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  • DOI: https://doi.org/10.1245/s10434-013-3161-9

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