Phase I study of a chloroquine–gemcitabine combination in patients with metastatic or unresectable pancreatic cancer
- 283 Downloads
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.
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).
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.
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.
KeywordsChloroquine Gemcitabine Pancreatic cancer Interferon-gamma receptor-1 Toll-like receptor 2 Beta-2 microglobulin
This work was supported by the Julius Müller Stiftung and the Kurt und Senta Hermann Stiftung.
Compliance with ethical standards
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.
This article does not contain any studies with animals performed by any of the authors.
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 was obtained from all individual participants included in the study.
- 12.Buch IN, Munz H, Pascolo C (2016) S. Schedule-dependent synergy of chloroquine with chemotherapy for anti-cancer treatment. Cancer Res Oncol 2(2):8Google Scholar
- 17.Alberts DS, Marth C, Alvarez RD, Johnson G, Bidzinski M, Kardatzke DR et al (2008) Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: results from a prospectively designed analysis of progression-free survival. Gynecol Oncol 109(2):174–181CrossRefPubMedGoogle Scholar