TY  - JOUR
TI  - 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
VL  - 215
AV  - public
Y1  - 2025/01/17/
N1  - © 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/).
ID  - discovery10202698
N2  - 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.
SN  - 0959-8049
PB  - Elsevier BV
UR  - https://doi.org/10.1016/j.ejca.2024.115162
JF  - European Journal of Cancer
KW  - Autophagy inhibitor
KW  -  Chemotherapy
KW  -  Concurrent and maintenance treatment
KW  -  Hydroxychloroquine
KW  -  Randomised trial
KW  -  Small cell lung cancer
A1  - Lee, Siow Ming
A1  - Hewish, Madeleine
A1  - Ahmed, Samreen
A1  - Papadatos-Pastos, Dionysis
A1  - Karapanagiotou, Eleni
A1  - Blackhall, Fiona
A1  - Ford, Amy
A1  - Young, Robin
A1  - Garcia, Angel
A1  - Arora, Arvind
A1  - Hollingdale, Abigail
A1  - Ahmad, Tanya
A1  - Forster, Martin
A1  - Greystoke, Alastair
A1  - Bremner, Fion
A1  - Rudd, Robin
A1  - Farrelly, Laura
A1  - Vaja, Simran
A1  - Hackshaw, Allan
ER  -