Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: a randomized phase II trial

被引:23
|
作者
Noguchi, Masanori [1 ,2 ]
Arai, Gaku [5 ]
Egawa, Shin [6 ]
Ohyama, Chikara [7 ,8 ]
Naito, Seiji [9 ]
Matsumoto, Kazumasa [10 ]
Uemura, Hirotsugu [11 ]
Nakagawa, Masayuki [12 ]
Nasu, Yasutomo [13 ]
Eto, Masatoshi [14 ]
Suekane, Shigetaka [2 ]
Sasada, Tetsuro [15 ]
Shichijo, Shigeki [1 ]
Yamada, Akira [3 ]
Kakuma, Tatsuyuki [4 ]
Itoh, Kyogo [1 ]
机构
[1] Kurume Univ, Sch Med, Canver Vaccine Ctr, 67 Asahi Machi, Kurume, Fukuoka 8300011, Japan
[2] Kurume Univ, Sch Med, Dept Urol, 67 Asahi Machi, Kurume, Fukuoka 8300011, Japan
[3] Kurume Univ, Sch Med, Canc Vaccines Res Ctr Innovat Canc Therapy, Kurume, Fukuoka, Japan
[4] Kurume Univ, Sch Med, Biostat Ctr, Kurume, Fukuoka, Japan
[5] Dokkyo Med Univ, Koshigaya Hosp, Dept Urol, Koshigaya, Japan
[6] Jikei Univ, Sch Med, Dept Urol, Tokyo, Japan
[7] Hirosaki Univ, Dept Urol, Grad Sch Med, Hirosaki, Aomori, Japan
[8] Hirosaki Univ, Sch Med, Hirosaki, Aomori, Japan
[9] Sanshinkai Hara Hosp, Fukuoka, Japan
[10] Kitasato Univ, Sch Med, Dept Urol, Sagamihara, Kanagawa, Japan
[11] Kinki Univ, Fac Med, Dept Urol, Osaka, Japan
[12] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Urol, Kagoshima, Japan
[13] Okayama Univ, Grad Sch Med, Dept Urol, Okayama, Japan
[14] Univ Kyushu, Grad Sch Med Sci, Dept Urol, Fukuoka, Japan
[15] Kanagawa Canc Ctr Res Inst, Yokohama, Kanagawa, Japan
关键词
Prostate cancer; Multiple-peptide vaccine; Immunotherapy; Docetaxel; Phase II trial; PEPTIDE VACCINE; INCREASED SURVIVAL; IMMUNOTHERAPY; CHEMOTHERAPY; MITOXANTRONE; PREDNISONE; ESTRAMUSTINE; RESPONSES; ANTI-PD-1; SAFETY;
D O I
10.1007/s00262-020-02498-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naive patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with >= 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.
引用
收藏
页码:847 / 857
页数:11
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