Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer
| Autor: | Jacquin Jones, William L. Dahut, James L. Gulley, Susan Halabi, Matteo Vergati, John J. Wright, Howard L. Parnes, James W. Hodge, Clara C. Chen, Lisa Skarupa, Seth M. Steinberg, Elizabeth C. Jones, Mary Pazdur, Philip M. Arlen, Kwong-Yok Tsang, Diane J. Poole, Jeffrey Schlom, Ravi A. Madan, Jack P. Higgins, Vittore Cereda |
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| Rok vydání: | 2009 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Immunology Antineoplastic Agents Docetaxel Kaplan-Meier Estimate Cancer Vaccines Article Metastasis Prostate cancer Antigens Neoplasm Internal medicine medicine Immunology and Allergy Humans Transgenes Prostvac Aged business.industry Poxviridae Cancer Granulocyte-Macrophage Colony-Stimulating Factor Prostatic Neoplasms Androgen Antagonists Nomogram Prostate-Specific Antigen medicine.disease Prognosis Vaccine therapy Prostate-specific antigen Taxoids Cancer vaccine business |
| Zdroj: | Cancer immunology, immunotherapy : CII. 59(5) |
| ISSN: | 1432-0851 |
| Popis: | A concurrent multicenter, randomized Phase II trial employing a recombinant poxviral vaccine provided evidence of enhanced median overall survival (OS) (p=0.0061) in patients with metastatic castrate-resistant prostate cancer (mCRPC). The study reported here employed the identical vaccine in mCRPC to investigate the influence of GM-CSF with vaccine, and the influence of immunologic and prognostic factors on median OS. Thirty-two patients were vaccinated once with recombinant vaccinia containing the transgenes for prostate-specific antigen (PSA) and three costimulatory molecules (TRICOM). Patients received boosters with recombinant fowlpox containing the same four transgenes. Twelve of 32 patients showed declines in serum PSA post-vaccination and 2/12 showed decreases in index lesions. Median OS was 26.6 months (predicted median OS by the Halabi nomogram was 17.4 months). Patients with greater PSA-specific T-cell responses showed a trend (p=0.055) toward enhanced survival. There was no difference in T-cell responses or survival in cohorts of patients receiving GM-CSF vs no GM-CSF. Patients with a Halabi predicted survival of < 18 months (median predicted 12.3 months) had an actual median OS of 14.6 months, while those with a Halabi predicted survival of ≥ 18 months (median predicted survival 20.9 months) will meet or exceed 37.3 months, with 12/15 patients living longer than predicted (p=0.035). Treg suppressive function was shown to decrease following vaccine in patients surviving longer than predicted, and increase in patients surviving less than predicted. This hypothesis-generating study provides evidence that patients with more indolent mCRPC (Halabi predicted survival ≥ 18 months) may best benefit from vaccine therapy. |
| Databáze: | OpenAIRE |
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