WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial

  • Takashi Miyatake
  • Yutaka Ueda
  • Akiko Morimoto
  • Takayuki Enomoto
  • Sumiyuki Nishida
  • Toshiaki Shirakata
  • Yoshihiro Oka
  • Akihiro Tsuboi
  • Yusuke Oji
  • Naoki Hosen
  • Shin-ichi Nakatsuka
  • Satoshi Morita
  • Junichi Sakamoto
  • Haruo Sugiyama
  • Tadashi Kimura
Original Paper

Abstract

Objective

The aim of the present study was to analyze the long-term survival effects of WT1 peptide vaccine, in addition to its anti-tumor effects and toxicity.

Methods

A phase II clinical trial was conducted during the period of 2004–2010 at Osaka University Hospital, Osaka, Japan. The patients who had gynecologic malignancies progressing against previous treatments received WT1 peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination was allowed to further continue, unless the patient’s condition became significantly worse due to the disease progression.

Results

Forty out of 42 patients, who met all the inclusion criteria, underwent WT1 peptide vaccine. Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a single case (3 %), respectively, and liver toxicity of grade 1 in a single case (3 %). The overall survival period was significantly longer in cases positive for the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the vaccination, compared to those negative for the DTH reaction (p = 0.023). Multivariate Cox proportional hazards analysis demonstrated that the adjusted hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04–7.19, p = 0.043).

Conclusion

WT1 peptide vaccine may be a potential treatment, with limited toxicity, for gynecologic malignancies that have become resistant to conventional therapies. Larger scale of clinical studies is required to establish the efficacy of the WT1 peptide vaccine for gynecologic malignancies.

Keywords

WT1 peptide immunotherapy Gynecologic malignancy Anti-tumor effect Survival Stable disease Toxicity 

Abbreviations

CR

Complete response

CT

Computed tomography

HLA

Human leukocyte antigen

HPV

Human papillomavirus

OS

Overall survival

PD

Progressive disease

PFS

Progression-free survival

PR

Partial response

PS

Performance status

RECIST

Response evaluation criteria in solid tumor

RR

Responsive rate

SD

Stable disease

TC

Paclitaxel and carboplatin

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Takashi Miyatake
    • 1
  • Yutaka Ueda
    • 1
  • Akiko Morimoto
    • 1
  • Takayuki Enomoto
    • 1
  • Sumiyuki Nishida
    • 2
  • Toshiaki Shirakata
    • 4
  • Yoshihiro Oka
    • 3
    • 5
  • Akihiro Tsuboi
    • 2
  • Yusuke Oji
    • 2
  • Naoki Hosen
    • 6
  • Shin-ichi Nakatsuka
    • 7
  • Satoshi Morita
    • 8
  • Junichi Sakamoto
    • 9
  • Haruo Sugiyama
    • 10
  • Tadashi Kimura
    • 1
  1. 1.Department of Obstetrics and GynecologyOsaka University Graduate School of MedicineOsakaJapan
  2. 2.Department of Cancer ImmunotherapyOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of Respiratory Medicine, Allergy and Rheumatic DiseasesOsaka University Graduate School of MedicineOsakaJapan
  4. 4.Department of Biomedical InformaticsOsaka University Graduate School of MedicineOsakaJapan
  5. 5.Department of Immunopathology WPI Immunology Frontier Research CenterOsaka UniversityOsakaJapan
  6. 6.Department of Cancer Stem Cell BiologyOsaka University Graduate School of MedicineOsakaJapan
  7. 7.Department of PathologyKansai Rosai HospitalAmagasakiJapan
  8. 8.Department of Clinical StatisticsYokohama City University Medical CenterYokohamaJapan
  9. 9.Department of Health and Community MedicineNagoya University Graduate School of MedicineNagoyaJapan
  10. 10.Department of Functional Diagnostic ScienceOsaka University Graduate School of MedicineOsakaJapan

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