Anti-inflammatory may help reduce chemo side effects

Researchers at The University of Queensland’s (UQ) Institute for Molecular Bioscience (IMB) may have discovered a way for future cancer patients, including children with leukaemia, to avoid chemotherapy’s worst and most debilitating side effects.

Professor Irina Vetter and Dr Hana Starobova made the discovery while studying how the chemotherapy drug vincristine — used to treat cervical, brain and lung cancers, leukaemia and non-Hodgkin’s lymphomas — causes sensory nerves to function abnormally.

“Unfortunately, chemo’s side effects are sometimes so terrible that people interrupt their treatment or end it, putting them at risk of succumbing to their cancer,” Prof Vetter said.

Dr Starobova said neuropathy is one of vincristine’s most unpleasant and severe side effects, causing tingling and numbness in hands and feet, pain and muscle weakness leading to limping.

“Where chemotherapy is concerned, neuropathic pain results from immune cells infiltrating the nerves and inflammation running wild,” Dr Starobova said.

“Unfortunately, these symptoms can persist long after treatment. The only way to ease them is to lower the vincristine dose, but this lowers the treatment’s effectiveness against the cancer.”

Prof Vetter said inflammation is a natural response in the body to injury or infection, but unchecked it can cause its own issues. She and Dr Starobova thought ‘turning off’ the inflammation that is one of the body’s natural reactions to vincristine might reduce its accompanying pain and unpleasant symptoms.

“We found the anti-inflammatory drug anakinra substantially reduced the awful nerve symptoms for which vincristine chemotherapy is known,” Prof Vetter said. Anakinra is an existing rheumatoid and juvenile arthritis treatment.

“Importantly, it did not reduce the effectiveness of the chemo,” Prof Vetter noted.

Prof Vetter said the finding was specific to vincristine and anakinra, although early findings suggested anakinra may help relieve symptoms of some other chemotherapy drugs.

“Reducing the chemo’s unpleasant symptoms ultimately will save lives and a lot of patient suffering,” she said.

The research was published in the Journal of Experimental Medicine and part funded by the Kids’ Cancer Project, with Chief Executive Owen Finegan saying the researchers’ choice to test a known and approved drug meant relatively fast translation to clinical use.

“This discovery will flow through to patients much more quickly than if the researchers had developed a completely new drug,” he said.

“This is likely to bring better treatment for kids with cancers including acute lymphoblastic leukaemia, sarcoma, medulloblastoma and neuroblastoma.

“We are delighted that these findings — initiated to help children — will also benefit adults.”

Prof Vetter and Dr Starobova have since joined forces with colleague Professor Kate Schroder, whose group focuses on inflammasomes — the molecular machines that trigger the immune response. The team’s next step will focus on how vincristine activates immune cells.

“Working together allows us to accelerate this research,” Prof Vetter said.

Image caption: Four-year-old Archer Bermingham still suffers from his 2019 vincristine treatment for leukaemia; doctors estimated the side effects would last eight years.

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