This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaufman, H. L. Articles by Weiner, L. M. Search for Related Content PubMed PubMed Citation Articles by Kaufman, H. L. Articles by Weiner, L. M.

Phase II Randomized Study of Vaccine Treatment of Advanced Prostate Cancer (E7897): A Trial of the Eastern Cooperative Oncology Group

From the Columbia University, New York, NY; Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center, Boston, MA; Cancer Institute of New Jersey, New Brunswick, NJ; Indiana University Medical Center, Indianapolis, IN; University of Pittsburgh, Pittsburgh, PA; National Cancer Institute, Bethesda, MD; University of Wisconsin, Madison, WI; and Fox Chase Cancer Center, Philadelphia, PA

Address reprint requests to Howard Kaufman, MD, Columbia University Medical Center, 177 Fort Washington Avenue, New York, NY 10032; e-mail: hlk2003{at}columbia.edu

PURPOSE: A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated.

PATIENTS AND METHODS: A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses.

RESULTS: The prime/boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1% demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells.

CONCLUSION: Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease.

This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA14958, CA80775, CA49883, CA39229, CA21076, CA49957, and by the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Preliminary results of this trial were presented at the 38th American Society of Clinical Oncology Annual Meeting, Orlando, FL, May 18–21, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				C. T. Garnett, J. Schlom, and J. W. Hodge Combination of Docetaxel and Recombinant Vaccine Enhances T-Cell Responses and Antitumor Activity: Effects of Docetaxel on Immune Enhancement Clin. Cancer Res., June 1, 2008; 14(11): 3536 - 3544. [Abstract] [Full Text] [PDF]

				J. L. Gulley, P. M. Arlen, K.-Y. Tsang, J. Yokokawa, C. Palena, D. J. Poole, C. Remondo, V. Cereda, J. L. Jones, M. P. Pazdur, et al. Pilot Study of Vaccination with Recombinant CEA-MUC-1-TRICOM Poxviral-Based Vaccines in Patients with Metastatic Carcinoma Clin. Cancer Res., May 15, 2008; 14(10): 3060 - 3069. [Abstract] [Full Text] [PDF]

				J. Schlom, J. L. Gulley, and P. M. Arlen Paradigm Shifts in Cancer Vaccine Therapy Experimental Biology and Medicine, May 1, 2008; 233(5): 522 - 534. [Abstract] [Full Text] [PDF]

				J. J. Nemunaitis Are Vaccines Making a Comeback in Non-Small-Cell Lung Cancer? J. Clin. Oncol., March 20, 2008; 26(9): 1402 - 1403. [Full Text] [PDF]

				J. Schlom, P. M. Arlen, and J. L. Gulley Immunotherapies with Other Therapeutic Modalities: New Paradigms for Clinical Trial Design ASCO Educational Book, January 1, 2008; 2008(1): 101 - 106. [Abstract] [Full Text] [PDF]

				J. Schlom, P. M. Arlen, and J. L. Gulley Cancer Vaccines: Moving Beyond Current Paradigms Clin. Cancer Res., July 1, 2007; 13(13): 3776 - 3782. [Abstract] [Full Text] [PDF]

				T. I. Naslund, C. Uyttenhove, E. K. L. Nordstrom, D. Colau, G. Warnier, M. Jondal, B. J. Van den Eynde, and P. Liljestrom Comparative Prime-Boost Vaccinations Using Semliki Forest Virus, Adenovirus, and ALVAC Vectors Demonstrate Differences in the Generation of a Protective Central Memory CTL Response against the P815 Tumor J. Immunol., June 1, 2007; 178(11): 6761 - 6769. [Abstract] [Full Text] [PDF]

				E. Jager, J. Karbach, S. Gnjatic, A. Neumann, A. Bender, D. Valmori, M. Ayyoub, E. Ritter, G. Ritter, D. Jager, et al. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients PNAS, September 26, 2006; 103(39): 14453 - 14458. [Abstract] [Full Text] [PDF]

				C. P. Tarassoff, P. M. Arlen, and J. L. Gulley Therapeutic vaccines for prostate cancer. Oncologist, May 1, 2006; 11(5): 451 - 462. [Abstract] [Full Text] [PDF]

				K. R. Lindsey, L. Gritz, R. Sherry, A. Abati, P. A. Fetsch, L. C. Goldfeder, M. I. Gonzales, K. A. Zinnack, L. Rogers-Freezer, L. Haworth, et al. Evaluation of Prime/Boost Regimens Using Recombinant Poxvirus/Tyrosinase Vaccines for the Treatment of Patients with Metastatic Melanoma Clin. Cancer Res., April 15, 2006; 12(8): 2526 - 2537. [Abstract] [Full Text] [PDF]

				K. J. Pienta and D. Bradley Mechanisms underlying the development of androgen-independent prostate cancer. Clin. Cancer Res., March 15, 2006; 12(6): 1665 - 1671. [Full Text] [PDF]

				P. M. Arlen, J. L. Gulley, C. Parker, L. Skarupa, M. Pazdur, D. Panicali, P. Beetham, K. Y. Tsang, D. W. Grosenbach, J. Feldman, et al. A Randomized Phase II Study of Concurrent Docetaxel Plus Vaccine Versus Vaccine Alone in Metastatic Androgen-Independent Prostate Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1260 - 1269. [Abstract] [Full Text] [PDF]

				R. D. Loberg, C. J. Logothetis, E. T. Keller, and K. J. Pienta Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype J. Clin. Oncol., November 10, 2005; 23(32): 8232 - 8241. [Abstract] [Full Text] [PDF]

				L. E. Raez, S. Fein, and E. R. Podack Lung Cancer Immunotherapy Clin. Med. Res., November 1, 2005; 3(4): 221 - 228. [Abstract] [Full Text] [PDF]

				H. L. Kaufman and C. R. Divgi Optimizing Prostate Cancer Treatment by Combining Local Radiation Therapy with Systemic Vaccination Clin. Cancer Res., October 1, 2005; 11(19): 6757 - 6762. [Full Text] [PDF]

				S. Yang, J. W. Hodge, D. W. Grosenbach, and J. Schlom Vaccines with Enhanced Costimulation Maintain High Avidity Memory CTL J. Immunol., September 15, 2005; 175(6): 3715 - 3723. [Abstract] [Full Text] [PDF]

				K. J. Pienta and D. C. Smith Advances in Prostate Cancer Chemotherapy: A New Era Begins CA Cancer J Clin, September 1, 2005; 55(5): 300 - 318. [Abstract] [Full Text] [PDF]

				J. L. Gulley, P. M. Arlen, A. Bastian, S. Morin, J. Marte, P. Beetham, K.-Y. Tsang, J. Yokokawa, J. W. Hodge, C. Menard, et al. Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3353 - 3362. [Abstract] [Full Text] [PDF]

				Y. Oka, A. Tsuboi, T. Taguchi, T. Osaki, T. Kyo, H. Nakajima, O. A. Elisseeva, Y. Oji, M. Kawakami, K. Ikegame, et al. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression PNAS, September 21, 2004; 101(38): 13885 - 13890. [Abstract] [Full Text] [PDF]