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. 2013 Nov;20(12):3787-93. doi: 10.1245/s10434-013-3161-9. Epub 2013 Aug 1.

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/m(2)) 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy*
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Follow-Up Studies
  • Humans
  • Laparoscopy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasm Staging
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Preoperative Care
  • Prognosis
  • Radiotherapy Dosage
  • Remission Induction
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • Deoxycytidine
  • Bevacizumab
  • gemcitabine