%0 Journal Article
%@ 0959-8049
%A Lee, Siow Ming
%A Hewish, Madeleine
%A Ahmed, Samreen
%A Papadatos-Pastos, Dionysis
%A Karapanagiotou, Eleni
%A Blackhall, Fiona
%A Ford, Amy
%A Young, Robin
%A Garcia, Angel
%A Arora, Arvind
%A Hollingdale, Abigail
%A Ahmad, Tanya
%A Forster, Martin
%A Greystoke, Alastair
%A Bremner, Fion
%A Rudd, Robin
%A Farrelly, Laura
%A Vaja, Simran
%A Hackshaw, Allan
%D 2025
%F discovery:10202698
%I Elsevier BV
%J European Journal of Cancer
%K Autophagy inhibitor, Chemotherapy, Concurrent and maintenance treatment, Hydroxychloroquine, Randomised trial, Small cell lung cancer
%T 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
%U https://discovery.ucl.ac.uk/id/eprint/10202698/
%V 215
%X 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 ≥ 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.
%Z © 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/).