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Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer

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Abstract

Second-line chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer has shown disappointing survival outcomes due to rapid disease progression and performance deterioration. The aim of this phase II trial was to evaluate the efficacy and safety of adoptive immunotherapy using ex vivo-expanded, cytokine-induced killer (CIK) cells in gemcitabine-refractory advanced pancreatic cancer. Patients with advanced pancreatic cancer who showed disease progression during gemcitabine-based chemotherapy were enrolled in this study. For generation of CIK cells, peripheral blood samples were collected from each patient and cultured with anti-CD3 monoclonal antibody and IL-2. Patients received CIK cells intravenously 10 times, every week for 5 weeks and then every other week for 10 weeks. Twenty patients were enrolled between November 2009 and September 2010. The disease control rate was 25 % (4/16 patients). The median progression-free survival (PFS) was 11.0 weeks (95 % CI 8.8–13.2), and the median overall survival (OS) was 26.6 weeks (95 % CI 8.6–44.6). Grade 3 toxicities included general weakness in two patients and thrombocytopenia in one patient. Grade 4 hematologic or non-hematologic toxicity was not observed. Patients showed improvement in pancreatic pain, gastrointestinal distress, jaundice, body image alterations, altered bowel habits, health satisfaction, and sexuality when assessing quality of life (QoL). Adoptive immunotherapy using CIK cells showed comparable PFS and OS to survival data of previous trials that assessed conventional chemotherapies while maintaining tolerability and showing encouraging results in terms of patient QoL in gemcitabine-refractory advanced pancreatic cancer (clinicalTrials.gov number NCT00965718).

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Abbreviations

CIK cells:

Cytokine-induced killer cells

CA 19-9:

Carbohydrate antigen 19-9

CIs:

Confidence intervals

DCR:

Disease control rate

ECOG-PS:

Eastern Cooperative Oncology Group performance status

EORTC:

European Organization for Research and Treatment of Cancer

FACS:

Fluorescence-activated cell sorting

HCC:

Hepatocellular carcinoma

INR:

International normalized ratio

ITT:

Intention-to-treat

MHC:

Major histocompatibility complex

OFF:

Oxaliplatin, folinic acid, and 5-FU

OS:

Overall survival

PBMCs:

Peripheral blood mononuclear cells

PD:

Progressive disease

PFS:

Progression-free survival

PP:

Per-protocol

QLQ-C30:

Quality of Life Questionnaire Core 30

QLQ-PAN26:

Quality of Life Questionnaire Core 30 in patients with pancreatic cancer

QoL:

Quality of life

SD:

Stable disease

VAS:

Visual analog scale

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea

    Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park & Si Young Song

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  1. Moon Jae Chung
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  2. Jeong Youp Park
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  3. Seungmin Bang
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Correspondence to Si Young Song.

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Chung, M.J., Park, J.Y., Bang, S. et al. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer. Cancer Immunol Immunother 63, 939–946 (2014). https://doi.org/10.1007/s00262-014-1566-3

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