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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients: prolongation of prostate-specific antigen doubling time

Authors: Masanori Noguchi, Fukuko Moriya, Shigetaka Suekane, Rei Ohnishi, Satoko Matsueda, Tetsuro Sasada, Akira Yamada, Kyogo Itoh

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC.

Methods

One hundred patients with progressive CRPC were treated with PPV using 2–4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied.

Results

PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis.

Conclusions

PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.

Trial registration

UMIN000001850
Appendix
Available only for authorised users
Literature
1.
Vollmer RT, Dawson NA, Vogelzang NJ: The dynamics of prostate specific antigen in hormone refractory prostate carcinoma: an analysis of cancer and leukemia group B study 9181 of megestrol acetate. Cancer. 1998, 83: 1989-1994. 10.1002/(SICI)1097-0142(19981101)83:9<1989::AID-CNCR15>3.0.CO;2-V.CrossRefPubMed
2.
Armstrong AJ, Garrett-Mayer E, Ou Yang YC, Carducci MA, Tannock I, de Wit R, Eisenberger M: Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol. 2007, 25: 3965-3970. 10.1200/JCO.2007.11.4769.CrossRefPubMed
3.
Scher HI, Kelly WM, Zhang ZF, Ouyang P, Sun M, Schwartz M, Ding C, Wang W, Horak ID, Kremer AB: Post-therapy serum prostate-specific antigen level and survival in patients with androgen-independent prostate cancer. J Natl Cancer Inst. 1999, 91: 244-251. 10.1093/jnci/91.3.244.CrossRefPubMed
4.
Petrylak DP, Ankerst DP, Jiang CS, Tangen CM, Hussain MH, Lara PN, Jones JA, Taplin ME, Burch PA, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED: Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99–16. Natl Cancer Inst. 2006, 98: 516-521. 10.1093/jnci/djj129.CrossRef
5.
Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, Humphrey R, Blumenstein B, Old L, Wolchok J: Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst. 2010, 102: 1388-1397. 10.1093/jnci/djq310.CrossRefPubMedPubMedCentral
6.
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF: IMPACT Study Investigators: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010, 363: 411-422. 10.1056/NEJMoa1001294.CrossRefPubMed
7.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA: TAX 327 Investigators: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004, 351: 1488-1490. 10.1056/NEJMp048178.CrossRef
8.
Petrylak DP, Tangen CM, Hussain MH, Lara PN, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004, 351: 1513-1520. 10.1056/NEJMoa041318.CrossRefPubMed
9.
Stein WD, Gulley JL, Schlom J, Madan RA, Dahut W, Figg WD, Ning YM, Arlen PM, Price D, Bates SE, Fojo T: Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res. 2011, 17: 907-917. 10.1158/1078-0432.CCR-10-1762.CrossRefPubMed
10.
Noguchi M, Kobayashi K, Suetsugu N, Tomiyasu K, Suekane S, Yamada A, Itoh K, Noda S: Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination. Prostate. 2003, 57: 80-92. 10.1002/pros.10276.CrossRefPubMed
11.
Noguchi M, Itoh K, Suekane S, Yao A, Suetsugu N, Katagiri K, Yamada A, Yamana H, Noda S: Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer. Cancer Sci. 2004, 95: 77-84. 10.1111/j.1349-7006.2004.tb03174.x.CrossRefPubMed
12.
Noguchi M, Itoh K, Suekane S, Morinaga A, Sukehiro A, Suetsugu N, Katagiri K, Yamada A, Noda S: Immunological monitoring during combination of patient-oriented peptide vaccination and estramustine phosphate in patients with metastatic hormone refractory prostate cancer. Prostate. 2004, 60: 32-45. 10.1002/pros.20011.CrossRefPubMed
13.
Noguchi M, Itoh K, Yao A, Mine T, Yamada A, Obata Y, Furuta M, Harada M, Suekane S, Matsuoka K: Immunological evaluation of individualized peptide vaccination with a low dose of estramustine for HLA-A24+ HRPC patients. Prostate. 2005, 63: 1-12. 10.1002/pros.20157.CrossRefPubMed
14.
Noguchi M, Mine T, Yamada A, Obata Y, Yoshida K, Mizoguchi J, Harada M, Suekane S, Itoh K, Matsuoka K: Combination therapy of personalized peptide vaccination and low-dose estramustine phosphate for metastatic hormone refractory prostate cancer patients: an analysis of prognostic factors in the treatment. Oncol Res. 2007, 16: 341-349.PubMed
15.
Noguchi M, Kakuma T, Uemura H, Nasu Y, Kumon H, Hirao Y, Moriya F, Suekane S, Matsuoka K, Komatsu N, Shichijo S, Yamada A, Itoh K: A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer. Cancer Immunol Immunother. 2010, 59: 1001-1009. 10.1007/s00262-010-0822-4.CrossRefPubMed
16.
Noguchi M, Uemura H, Naito S, Akaza H, Yamada A, Itoh K: A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. Prostate. 2011, 71: 470-479. 10.1002/pros.21261.CrossRefPubMed
17.
Matsumoto K, Noguchi M, Satoh T, Tabata K, Fujita T, Iwamura M, Yamada A, Komatsu N, Baba S, Itoh K: A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin. BJU Int. 2011, 108: 831-838.CrossRefPubMed
18.
Yoshiyama K, Terazaki Y, Matsueda S, Shichijo S, Noguchi M, Yamada A, Mine T, Ioji T, Itoh K, Shirouzu K, Sasada T, Takamori S: Personalized peptide vaccination in patients with refractory non-small cell lung cancer. Int J Oncol. 2012, 24: 795-801.
19.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumor: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000, 92: 205-216. 10.1093/jnci/92.3.205.CrossRefPubMed
20.
Komatsu N, Shichijo S, Nakagawa M, Itoh K: New multiplexed flow cytometric assay to measure anti-peptide antibody: a novel tool for monitoring immune responses to peptides used for immunization. Scand J Cin Lab Invest. 2004, 64: 1-11. 10.1080/00365510310003391.CrossRef
21.
Scher HI, Halabi S, Tannoch I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M, Prostate Cancer Clinical Trials Working Group: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008, 226: 1148-1159.CrossRef
22.
McNeel DG, Dunphy E, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R, Liu G, Eickhoff JC, Wilding G: Safety and immunological efficacy of a DNA vaccine encoding prostatic and phosphatase in patients with D0 prostate cancer. J Clin Oncol. 2009, 27: 4047-4054. 10.1200/JCO.2008.19.9968.CrossRefPubMedPubMedCentral
23.
Sweeney C, Liu G, Yiannoutsos C, Kolesar J, Horvath D, Staab MJ, Fife K, Armstrong V, Treston A, Sidor C, Wilding G: A phase II, multicenter, randomized, double-blind, safety trial assessing the pharmacokinetics, pharmacodynamics, and efficacy of oral 2-methoxyestradiol capsules in hormone-refractory prostate cancer. Clin Cancer Res. 2005, 11: 6625-6633. 10.1158/1078-0432.CCR-05-0440.CrossRefPubMed
24.
De Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO: TROPIC Investigators: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial. Lancet. 2010, 376: 1147-1154. 10.1016/S0140-6736(10)61389-X.CrossRefPubMed
25.
De Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI, COU-AA-301 Investigators: Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011, 364: 1995-2005. 10.1056/NEJMoa1014618.CrossRefPubMedPubMedCentral
Metadata
Title
A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients: prolongation of prostate-specific antigen doubling time
Authors
Masanori Noguchi
Fukuko Moriya
Shigetaka Suekane
Rei Ohnishi
Satoko Matsueda
Tetsuro Sasada
Akira Yamada
Kyogo Itoh
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-613

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