Panagiotis Samaras1, Marina Tusup2, Thi Dan Linh Nguyen-Kim3, Burkhardt Seifert4, Helga Bachmann1, Roger von Moos1, Alexander Knuth1,5, Steve Pascolo6,7,7. 1. Department of Oncology, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland. 2. Department of Dermatology, University Hospital of Zürich, Gloriastrasse 31, 8091, Zurich, Switzerland. 3. Department of Diagnostic and Interventional Radiology, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland. 4. Department of Biostatistics at the Epidemiology, Biostatistics and Prevention Institute, University of Zürich, Zurich, Switzerland. 5. National Center for Cancer Care and Research NCCCR, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar. 6. Department of Oncology, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland. steve.pascolo@usz.ch. 7. Department of Dermatology, University Hospital of Zürich, Gloriastrasse 31, 8091, Zurich, Switzerland. steve.pascolo@usz.ch.
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.
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.
Authors: Jan Hraběta; Marie Belhajová; Hana Šubrtová; Miguel Angel Merlos Rodrigo; Zbyněk Heger; Tomáš Eckschlager Journal: Int J Mol Sci Date: 2020-06-20 Impact factor: 5.923
Authors: María Inés Molejon; Mirna Swayden; Daniele Fanale; Jennifer Bintz; Odile Gayet; Philippe Soubeyran; Juan Iovanna Journal: Oncotarget Date: 2018-07-20