Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer

PLoS One. 2012;7(1):e29794. doi: 10.1371/journal.pone.0029794. Epub 2012 Jan 17.

Abstract

Background: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

Methods and findings: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.

Conclusions: These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.

Trial registration: Clinicaltrials.gov NCT00954525.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Pulmonary Embolism / chemically induced
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Treatment Outcome

Substances

  • Quinazolines
  • Deoxycytidine
  • gemcitabine
  • Erlotinib Hydrochloride
  • Ascorbic Acid

Associated data

  • ClinicalTrials.gov/NCT00954525