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Lookup NU author(s): Professor Alastair GreystokeORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The AuthorsBackground: 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.
Author(s): Lee SM, Hewish M, Ahmed S, Papadatos-Pastos D, Karapanagiotou E, Blackhall F, Ford A, Young R, Garcia A, Arora A, Hollingdale A, Ahmad T, Forster M, Greystoke A, Bremner F, Rudd R, Farrelly L, Vaja S, Hackshaw A
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Year: 2025
Volume: 215
Print publication date: 17/01/2025
Online publication date: 06/12/2024
Acceptance date: 02/04/2018
Date deposited: 08/01/2025
ISSN (print): 0959-8049
ISSN (electronic): 1879-0852
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.ejca.2024.115162
DOI: 10.1016/j.ejca.2024.115162
Data Access Statement: On request, the anonymised clinical data can be made available to research groups with an appropriate research plan.
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