Cervical cancer patients were significantly more likely to be alive and cancer-free after five years when given a short course of chemotherapy prior to chemoradiation, finds a clinical trial led by researchers from UCL and UCLH.
Chemoradiation (CRT), a combination of chemotherapy and radiotherapy, has been the standard treatment for cervical cancer since 1999, but despite improvements in radiation therapy techniques cancer returns in up to 30% of cases1.
The INTERLACE phase III trial, funded by Cancer Research UK and UCL Cancer Trials Centre, assessed whether a short course of induction chemotherapy (IC) prior to CRT could reduce the rate of relapse and death among patients with advanced cervical cancer that hasn't spread to other parts of the body.
Treatment with IC followed by CRT led to a 40% reduction in the risk of death and a 35% reduction in the risk of cancer returning over a follow-up period of at least five years.
The researchers say the results, published in The Lancet, demonstrate that this approach has a clear benefit for patients and should be incorporated into national and international clinical guidelines.
Dr Mary McCormack, lead investigator of the trial from UCL Cancer Institute and UCLH, said: "A short course of induction chemotherapy prior to standard chemoradiation treatment greatly boosts overall survival and reduces the risk of relapse in patients with locally advanced cervical cancer.
"This approach is a straightforward way to make a positive difference, using existing drugs that are cheap and already approved for use in patients. It has already been adopted by some cancer centres and there's no reason that this shouldn't be offered to all patients undergoing chemoradiation for this cancer."
The trial team recruited 500 patients over 10 years from hospitals in the UK, Mexico, India, Italy and Brazil. Those who participated in the study had been diagnosed with cervical cancer, which was too large to be treated by a surgical operation but had not yet spread to other parts of the body. The median age of patients in the trial was 46.
Patients were randomly allocated to receive either standard CRT (external radiation with weekly cisplatin and brachytherapy), or an initial six-week course of IC (carboplatin and paclitaxel chemotherapy) followed by standard CRT2.
After five years, 80% of those who received IC plus CRT were alive and 73% had not seen their cancer return or spread. In the standard treatment group, 72% were alive and 64% had not seen their cancer return or spread.
This equates to a 40% reduction in the risk of death and a 35% reduction in the risk of cancer returning. Five patients involved in the trial have been disease-free for over 10 years.
Unlike most cancers, cervical cancer is a disease that affects women who are relatively young. The peak incidence of cervical cancer is in women in their early thirties, with around 3,200 new cases each year in the UK. The five-year survival rate for cervical cancer stands at around 70%.
Abbie Halls, from London, was diagnosed with locally-advanced cervical cancer at the age of 27. She took part in the INTERLACE trial and received IC followed by CRT instead of the standard treatment.
"Being diagnosed with cancer at such a young age was completely unexpected, a bit surreal and completely terrifying. I'd just started a new career in London and it felt like my whole life had been put on hold. There was a fairly good chance that the standard treatment would work, but you can't help thinking about what happens if it doesn't work, or if the cancer returns.
"I wasn't sure that I wanted to take part in the trial at first, as it meant more treatment and side effects like hair loss, without knowing if it would help. But I decided to do it and it went really well. I've been cancer-free for over nine years now and I'm not sure if I'd be here without the treatment that I received. I'm happy that I could play a part in advancing the research, which I hope is going to save the lives of many more women in years to come."
Professor Jonathan Ledermann, senior author of the study from UCL Cancer Institute, said: "Cervical cancer is a disease that often strikes women in their thirties or younger. Those with locally advanced disease have a relatively high chance of relapse and the disease can take a huge toll on patients and their families. The incremental cost for using the drugs in the INTERLACE trial is low, making this a new treatment that can be easily implemented in all health economies, to significantly improve overall survival."
Although IC with CRT therapy is already in use in some cancer centres, following these peer-reviewed trial results researchers now expect the approach to be incorporated into national and international clinical guidelines, which will make it easier for hospitals to offer this treatment to patients.
Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said: "Timing is everything when you're treating cancer. The simple act of adding induction chemotherapy to the start of chemoradiation treatment for cervical cancer has delivered remarkable results in the INTERLACE trial.
"A growing body of evidence is showing that additional chemotherapy before other treatments, like surgery and radiotherapy, can improve the chances of successful treatment for patients. Not only can it reduce the chances of cancer coming back, it can also be delivered quickly, using drugs already available worldwide.
"Clinical trials like INTERLACE shows how UK science can have global impact. We need to keep making the UK a more attractive place to run large-scale clinical trials like INTERLACE, or we risk falling behind our international peers.
"We're excited for the improvements this trial could bring to cervical cancer treatment and hope short courses of induction chemotherapy will be rapidly adopted in the clinic."
Preliminary results from INTERLACE were presented at the European Society for Medical Oncology (ESMO) congress on Sunday 22 October 2023.
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