Researchers at UCLH and UCL have completed the first and only randomised trial to explore a new approach to treating aggressive lung cancer.
The trial drug, hydroxychloroquine (HCQ), was found not to benefit patients with small cell lung cancer (SCLC), a highly aggressive form of lung cancer that accounts for about 10-15% of all lung cancers.
However, the trial, known as Study 15 and sponsored by UCL, provides important findings on both the potential and limitations of HCQ in cancer treatment.
The study also highlights the need to carefully evaluate where HCQ can and cannot be repurposed for lung cancer treatment. HCQ was previously proposed as a treatment for Covid-19, but found not to be effective for this use.
HCQ is a medication originally used to treat malaria and autoimmune diseases, and it gained attention during the COVID-19 pandemic as a potential treatment for COVID-19. One of its main properties is its ability to inhibit autophagy.
Autophagy is the normal process by which cells break down and recycle old or damaged parts. While it is crucial for normal cell function, cancer cells can exploit autophagy to provide them with energy under stressful conditions, such as after chemotherapy, allowing them to survive, grow and resist treatments.
It was thought that by inhibiting autophagy with drugs like HCQ, cancer cells could be deprived of one method of survival and replication. However, the results of Study 15 suggest that this approach may not be effective clinically, despite promising preclinical lab findings.
The trial, supported by the BRC, involved 72 patients, with 36 receiving chemotherapy plus HCQ and 36 receiving chemotherapy alone. The results showed that HCQ did not improve survival rates.
In addition, patients receiving HCQ experienced more side effects, such as nausea and vomiting, and fewer patients completed four cycles of chemotherapy. Evidence from other smaller studies, including those in non-small cell lung cancer, also suggests a potentially limited role for HCQ.
Professor Siow-Ming Lee, Chief Investigator and designer of the study, said: “Our findings highlight the importance of evidence-based research in repurposing HCQ as an anti-cancer agent. While some progress has been made recently in treating small cell lung cancer with chemotherapy combined with immunotherapy, most patients still relapse, and the search for more effective therapies for SCLC must continue.”
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