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. 2017 Sep;46(8):994-1002.
doi: 10.1097/MPA.0000000000000880.

Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy

Hiroto Matsui  1 , Shoichi Hazama, Kazuhiko Sakamoto, Yoshitaro Shindo, Shinsuke Kanekiyo, Masao Nakashima, Satoshi Matsukuma, Yoshihiro Tokuhisa, Michihisa Iida, Nobuaki Suzuki, Kiyoshi Yoshimura, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Masaaki Oka, Hiroaki Nagano
Affiliations

Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy

Hiroto Matsui et al. Pancreas. 2017 Sep.

Abstract

Objectives: We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer.

Methods: A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM. After surgery, MUC1-CTLs were induced and administered intravenously 3 times, and GEM administered according to the standard regimen for 6 months. The patients whose relative dose intensity of GEM was 50% or more and who received 2 or more MUC1-CTL treatments were used as the adequate treatment group (n = 21).

Results: In the adequate treatment group, disease-free survival was 15.8 months, and overall survival was 24.7 months. Liver metastasis was found only in 7 patients (33%), and local recurrence occurred in 4 patients (19%). The independent prognostic factor of long-term disease-free survival on multivariate analysis was the average number of CTLs administered (P = 0.0133).

Conclusions: The combination therapy with AIT and GEM prevented liver metastasis and local recurrence. Moreover, the disease free-survival was improved in patients who received sufficient CTLs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Treatment regimen of postoperative AIT with MUC1-CTL plus GEM for pancreatic cancer. POD indicates postoperative day.
FIGURE 2
FIGURE 2
Induction of MUC1-CTLs. MUC1-CTLs were induced by coculture with YPK-1, a human pancreatic cancer cell line, and then with IL-2. MMC, mitomycin C; rhIL-2, recombinant human interleukin 2; JRU, Japan reference unit.
FIGURE 3
FIGURE 3
Flowchart of the study population.
FIGURE 4
FIGURE 4
Kaplan-Meier curves for DFS. A, The adequate treatment group. B, The inadequate treatment group.
FIGURE 5
FIGURE 5
Kaplan-Meier curves for OS. A, The adequate treatment group. B, The inadequate treatment group.
FIGURE 6
FIGURE 6
Kaplan-Meier curves compared by average number of administered CTLs. A, DFS. B, OS.
See this image and copyright information in PMC

References

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