eprintid: 10202698
rev_number: 9
eprint_status: archive
userid: 699
dir: disk0/10/20/26/98
datestamp: 2025-01-03 17:02:03
lastmod: 2025-01-03 17:02:03
status_changed: 2025-01-03 17:02:03
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Lee, Siow Ming
creators_name: Hewish, Madeleine
creators_name: Ahmed, Samreen
creators_name: Papadatos-Pastos, Dionysis
creators_name: Karapanagiotou, Eleni
creators_name: Blackhall, Fiona
creators_name: Ford, Amy
creators_name: Young, Robin
creators_name: Garcia, Angel
creators_name: Arora, Arvind
creators_name: Hollingdale, Abigail
creators_name: Ahmad, Tanya
creators_name: Forster, Martin
creators_name: Greystoke, Alastair
creators_name: Bremner, Fion
creators_name: Rudd, Robin
creators_name: Farrelly, Laura
creators_name: Vaja, Simran
creators_name: Hackshaw, Allan
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
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D19
divisions: H01
keywords: Autophagy inhibitor, Chemotherapy, Concurrent and maintenance treatment, Hydroxychloroquine, Randomised trial, Small cell lung cancer
note: © 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/).
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 ≥ 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.
date: 2025-01-17
date_type: published
publisher: Elsevier BV
official_url: https://doi.org/10.1016/j.ejca.2024.115162
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2344341
doi: 10.1016/j.ejca.2024.115162
medium: Print-Electronic
pii: S0959-8049(24)01769-6
lyricists_name: Hackshaw, Allan
lyricists_name: Lee, Siow-Ming
lyricists_name: Vaja, Simran
lyricists_id: AHACK11
lyricists_id: MSLEE39
lyricists_id: SVAJA98
actors_name: Hackshaw, Allan
actors_id: AHACK11
actors_role: owner
full_text_status: public
publication: European Journal of Cancer
volume: 215
article_number: 115162
event_location: England
issn: 0959-8049
citation:        Lee, Siow Ming;    Hewish, Madeleine;    Ahmed, Samreen;    Papadatos-Pastos, Dionysis;    Karapanagiotou, Eleni;    Blackhall, Fiona;    Ford, Amy;                                                 ... Hackshaw, Allan; + view all <#>        Lee, Siow Ming;  Hewish, Madeleine;  Ahmed, Samreen;  Papadatos-Pastos, Dionysis;  Karapanagiotou, Eleni;  Blackhall, Fiona;  Ford, Amy;  Young, Robin;  Garcia, Angel;  Arora, Arvind;  Hollingdale, Abigail;  Ahmad, Tanya;  Forster, Martin;  Greystoke, Alastair;  Bremner, Fion;  Rudd, Robin;  Farrelly, Laura;  Vaja, Simran;  Hackshaw, Allan;   - view fewer <#>    (2025)    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.                   European Journal of Cancer , 215     , Article 115162.  10.1016/j.ejca.2024.115162 <https://doi.org/10.1016/j.ejca.2024.115162>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10202698/3/Hackshaw_1-s2.0-S0959804924017696-main.pdf