Arsenic trioxide in patients with adenocarcinoma of the pancreas refractory to gemcitabine: a phase II trial of the University of Chicago Phase II Consortium

Am J Clin Oncol. 2008 Dec;31(6):553-6. doi: 10.1097/COC.0b013e318178e4cd.

Abstract

Objectives: There is no effective therapy for patients with metastatic pancreatic cancer who fail initial therapy with gemcitabine. Arsenic trioxide has potent antiproliferative and proapoptotic effects in pancreatic cancer cell lines. We conducted a multicenter phase II trial in patients with advanced pancreatic cancer who experienced disease progression on or after a gemcitabine-containing regimen.

Methods: Arsenic trioxide 0.3 mg/kg was administered intravenously over 1 hour daily for 5 consecutive days every 28 days. Restaging computed tomography scans were obtained every 2 cycles.

Results: Thirteen patients were enrolled between December 2002 and November 2003. Twenty-four cycles were administered (median 2; range 1-2). There were no grade 3/4 hematologic toxicities; grade 1/2 anemia and leukopenia occurred in 50% and 25% of patients, respectively. Grade 3 toxicities included fatigue and thrombosis in 17% of patients. Only 1 patient developed a prolongation of the QTc interval. There were no objective responses. Median progression-free survival was 1.6 months (95% confidence interval, 1.2-1.9). Median survival was 3.8 months (95% confidence interval, 1.6-6.8).

Conclusions: Despite promising in vitro data, arsenic trioxide has no activity in pancreatic cancer patients who develop progressive disease after gemcitabine. Multicenter phase II trials are feasible in this patient population, and novel agents are clearly needed.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Arsenic Trioxide
  • Arsenicals / therapeutic use*
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy
  • Oxides / therapeutic use*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Salvage Therapy*
  • Survival Rate
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Deoxycytidine
  • gemcitabine
  • Arsenic Trioxide