A randomized trial of personalized peptide vaccine (PPV) plus low-dose estramustine (EMP) versus full-dose EMP in patients .....

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Author(s): M. Noguchi,
H. Uemura, H. Kumon, Y. Nasu, Y. Hirao, K. Matsuoka, T. Kakuma, A.
Yamada, K. Itoh; Kurume University School of Medicine, Kurume, Japan;
Kinki University School of Medicine, Kyoyama, Japan; Okayama
University, Okayama, Japan; Nara University School of Medicine,
Kashihabarea, Japan
Background: Personalized
selection of the right peptides for each patient could be a novel
peptide-based immunotherapy for boosting anti-cancer immunity in many
patients (pts). This randomized study evaluated the anti-tumor effect
and safety of PPV plus a low-dose EMP compared with full dose EMP for
patients with hormone-refractory prostate cancer (HRPC).
This was a randomized (1:1), open labeled, cross-over study in pts with
HRPC. Pts were randomized to arm A; PPV plus low-dose EMP (280 mg/day)
or arm B; full dose EMP (560 mg/day) according to age and PSA levels.
In arm A, prevaccination plasma were measured for their IgG levels for
each of the 14 or 12 candidate peptides which can induce HLA-A2 or
A24-restricted CTL activity against cancer cells followed by biweekly
subcutaneous administration of the top four peptides (3mg each) showing
the strongest IgG responses. Disease progression (PD) was defined as
three consecutive and 125% increase from baseline PSA levels at least
two weeks apart or objective PD by RECIST criteria. After PD, pts were
treated with the opposite regime. The primary endpoint was
progression-free survival (PFS), and the secondary endpoints were
overall survival and toxicity. The planned sample size was 80.
A total of 54 pts from 4 institutions were enrolled between June 2006
and December 2008. The accural into arms A and B was 27 and 27 pts,
respectively. The main pts characteristics are (arm A/B): median age
71/69 years, EOCG performance status 0/1 96%/4% and 100%/0%, HLA
A2/A24/A2A24 40%/32%/28% and 54%/27%/19%, median PSA 27/25 ng/ml, and
metastatic HRPC 96%/85%. All pts were evaluable for their response at
the time of interim analysis. The personalized peptide vaccination was
well tolerated with no major adverse effects. Increased levels of IgG
responses to the vaccinated peptides were observed in 20 of 23 (87%)
patients tested. The median PFS time was 246 days in the arm A group
and 85 days in the arm B, respectively. The PFS time in the arm A was
statistically longer than that in the arm B (log-rank test: p = 0.0007,
hazard ratio: 0.27, 95%CI: 0.12 to 0.615).
Conclusions: PPV plus low-dose EMP was associated with improvement in PSA-based PFS compared to full-dose EMP alone.