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Phase I study of a chloroquine–gemcitabine combination in patients with metastatic or unresectable pancreatic cancer

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Abstract

Purpose

Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine–chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer.

Methods

In this 3 + 3 dose escalation study, patients received a single weekly standard dose of intravenous gemcitabine, followed by single weekly oral intake of 100, 200 or 300 mg of chloroquine. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Immune status was evaluated by RT-PCR to measure the relative expression of immune-related genes in peripheral blood mononuclear cells (PBMCs).

Results

Overall, nine patients [median age 72 years; interquartile range (IQR), 68–78 years] were treated. No dose-limiting toxicities as defined in the protocol were observed. Three patients experienced partial response, and two patients had stable disease. The median time to progression was 4 months (95% CI 0.8–7.2), and the median overall survival was 7.6 months (95% CI 5.3–9.9). Among 86 assayed immune genes, three were significantly differentially expressed in PBMCs from responding versus non-responding patients: interferon-gamma receptor-1, toll-like receptor 2, and beta-2 microglobulin.

Conclusions

The addition of chloroquine to gemcitabine was well tolerated and showed promising effects on the clinical response to the anti-cancer chemotherapy. Based on these initial results, the efficacy of the gemcitabine–chloroquine combination should be further assessed.

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Acknowledgements

This work was supported by the Julius Müller Stiftung and the Kurt und Senta Hermann Stiftung.

Author information

Author notes

  1. Alexander Knuth

    Present address: National Center for Cancer Care and Research NCCCR, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

  2. Steve Pascolo

    Present address: Department of Dermatology, University Hospital of Zürich, Gloriastrasse 31, 8091, Zurich, Switzerland

Authors and Affiliations

  1. Department of Oncology, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland

    Panagiotis Samaras, Helga Bachmann, Roger von Moos, Alexander Knuth & Steve Pascolo

  2. Department of Dermatology, University Hospital of Zürich, Gloriastrasse 31, 8091, Zurich, Switzerland

    Marina Tusup & Steve Pascolo

  3. Department of Diagnostic and Interventional Radiology, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland

    Thi Dan Linh Nguyen-Kim

  4. Department of Biostatistics at the Epidemiology, Biostatistics and Prevention Institute, University of Zürich, Zurich, Switzerland

    Burkhardt Seifert

Authors
  1. Panagiotis Samaras
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  2. Marina Tusup
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  3. Thi Dan Linh Nguyen-Kim
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  4. Burkhardt Seifert
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  5. Helga Bachmann
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  6. Roger von Moos
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  7. Alexander Knuth
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  8. Steve Pascolo
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Corresponding author

Correspondence to Steve Pascolo.

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Funding

This study was funded by the University Hospital of Zürich, the Julius Müller Stiftung and the Kurt und Senta Hermann Stiftung.

Conflict of interest

Authors Samaras, Nguyen-Kim, Seifert, Bachmann, Knuth and Pascolo declare that they have no conflict of interest. Author von Moos is a participant in an advisory board of Elli Lilly.

Animals

This article does not contain any studies with animals performed by any of the authors.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the local Ethics Committee and Swissmedic (ClinicalTrials.gov identifier: NCT01777477) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Samaras, P., Tusup, M., Nguyen-Kim, T.D.L. et al. Phase I study of a chloroquine–gemcitabine combination in patients with metastatic or unresectable pancreatic cancer. Cancer Chemother Pharmacol 80, 1005–1012 (2017). https://doi.org/10.1007/s00280-017-3446-y

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  • DOI: https://doi.org/10.1007/s00280-017-3446-y

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