A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma

Ann Surg. 2014 Jul;260(1):142-8. doi: 10.1097/SLA.0000000000000251.

Abstract

Background: The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined.

Objective: We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma.

Methods: Eligible patients were screened using computed tomography-pancreas angiography, laparoscopy, endoscopic ultrasonography, and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100 minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks. Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiological, tumor marker and pathological response to neoadjuvant therapy, time to recurrence, patterns of failure, and feasibility of obtaining preoperative core biopsies.

Results: Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%), of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% confidence interval: 17-NA) and the median disease-specific survival was 30.6 months (95% confidence interval: 19-NA).

Conclusions: This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. Clinical trials identification: NCT00536874.

Publication types

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

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Pancreatectomy / methods*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / therapy*
  • Retrospective Studies
  • Ribonucleotide Reductases / antagonists & inhibitors
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Ribonucleotide Reductases
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00536874