@article{discovery10202698,
            year = {2025},
         journal = {European Journal of Cancer},
       publisher = {Elsevier BV},
           title = {Hydroxychloroquine in combination with platinum doublet chemotherapy as first-line treatment for extensive-stage small cell lung cancer (Study 15): A randomised phase II multicentre trial},
          volume = {215},
            note = {{\copyright} 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).},
           month = {January},
          author = {Lee, Siow Ming and Hewish, Madeleine and Ahmed, Samreen and Papadatos-Pastos, Dionysis and Karapanagiotou, Eleni and Blackhall, Fiona and Ford, Amy and Young, Robin and Garcia, Angel and Arora, Arvind and Hollingdale, Abigail and Ahmad, Tanya and Forster, Martin and Greystoke, Alastair and Bremner, Fion and Rudd, Robin and Farrelly, Laura and Vaja, Simran and Hackshaw, Allan},
            issn = {0959-8049},
             url = {https://doi.org/10.1016/j.ejca.2024.115162},
        abstract = {BACKGROUND: Most patients with small-cell lung cancer (SCLC) present with extensive-stage (ES) disease and have a poor prognosis despite achieving high initial response rates to platinum-based doublet chemotherapy. This study evaluated whether adding hydroxychloroquine (HCQ) to chemotherapy could improve outcomes. METHODS: This was a randomised multicentre phase II trial. Eligible patients had untreated ES-SCLC, a performance status 0-2 and measurable disease. Patients were randomly assigned (1:1 ratio) to HCQ (400�mg orally twice daily) plus carboplatin-gemcitabine or carboplatin-etoposide alone. Chemotherapy was administered for up to six cycles, with HCQ given concurrently and then as single agent for up to 30 months. Primary endpoint was PFS, aiming for a hazard ratio (HR) of 0.70. RESULTS: 72 patients were randomised (36 HCQ+chemotherapy and 36 chemotherapy alone). Median HCQ treatment duration was 4.4 months. HCQ did not improve PFS (HR 1.12 95�\%CI 0.69-1.84; p�=�0.64), with a median of 5.7 months (HCQ+chemotherapy) versus 6.2 months (chemotherapy). The corresponding median OS were 8.9 and 10.2 months (HR 0.83, 95�\%CI 0.48-1.45, p�=�0.52). Fewer patients in the HCQ arm completed four cycles of chemotherapy due to adverse events (64�\% vs. 81�\%). Grade {$\ge$}�3 adverse events were higher in the HCQ+chemotherapy arm (83.3�\% vs. 27.8�\%), primarily anaemia, neutropenia, and thrombocytopenia, partly due to the initially higher gemcitabine dose used CONCLUSIONS: Combining HCQ with platinum doublet chemotherapy did not improve PFS or OS outcomes for ES-SCLC, resulting in more patients stopping chemotherapy due to increased adverse events. When considered alongside other randomised studies of HCQ in cancer, the evidence collectively indicates a limited role for HCQ as a therapeutic option.},
        keywords = {Autophagy inhibitor, Chemotherapy, Concurrent and maintenance treatment, Hydroxychloroquine, Randomised trial, Small cell lung cancer}
}