Long-term administration of Wilms tumor-1 peptide vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites

Jpn J Clin Oncol. 2010 Dec;40(12):1184-8. doi: 10.1093/jjco/hyq112. Epub 2010 Jul 22.

Abstract

The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1-2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4-8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / secondary
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / radiotherapy
  • Bone Neoplasms / secondary
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects*
  • Cancer Vaccines / immunology
  • Cell Cycle Proteins
  • Chemotherapy, Adjuvant
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / secondary
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Dermatitis / etiology*
  • Dermatitis / immunology
  • Drug Administration Schedule
  • Female
  • Gallbladder Neoplasms / pathology
  • Humans
  • Injections, Intradermal / adverse effects
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Lymphocytes / immunology
  • Nuclear Proteins / administration & dosage*
  • Nuclear Proteins / adverse effects*
  • Nuclear Proteins / immunology
  • Palliative Care / methods
  • RNA Splicing Factors
  • Radiotherapy, Adjuvant
  • Skin / drug effects*
  • Skin / immunology

Substances

  • Antimetabolites, Antineoplastic
  • Cancer Vaccines
  • Cell Cycle Proteins
  • Nuclear Proteins
  • RNA Splicing Factors
  • WTAP protein, human
  • Deoxycytidine
  • gemcitabine