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New standard of care for advanced nose cancer patients
Advanced nose cancer patients benefit from new standard treatment after clinical trial at NCCS and China’s cancer centre

A new global standard treatment for high-risk locally advanced nose cancer has been established based on the findings from a multi-centre collaborative clinical trial.

The research team has found that giving chemotherapy first for three cycles before concurrent chemo-radiotherapy to these patients, as compared to giving chemo-radiotherapy alone, will reduce the likelihood of cancer relapse and improve survival.

The trial reported its 3-year results showing that one in 10 patients will avoid a relapse with this new treatment, and one in 20 patients will live longer as a consequence.

The trial was conducted by a multi-centre collaborative trial network for nose cancer that includes several participating sites in China and the National Cancer Centre Singapore (NCCS), led by the Sun Yat-sen University Cancer Center (SYSUCC) in Guangzhou, China.

The study is co-published in The New England Journal of Medicine.

Nose cancer, also known as Nasopharynx cancer, is the eighth most frequent cancer in males in Singapore, and predominantly affects the Chinese race, in particular the Cantonese, Teochew and Hokkien dialect groups. About two-thirds of patients are diagnosed with stage three and four nose cancers at the time of presentation. This means the cancer has grown outside of the nasal cavity to involve the bones at the skull base and/or into the brain. Nose cancer also has the propensity to spread to the neck lymph nodes, and in these high-risk advanced cases, both sides of the neck nodes and/or large neck nodes (>6 cm) are present.

Currently, the standard treatment for this subgroup of high-risk patients is concurrent chemo-radiotherapy; this usually entails seven weeks of precise high-dose radiotherapy using intensity modulated radiotherapy (IMRT) techniques, and cisplatin (chemotherapy) is given once a week or every three weeks with IMRT.

“Although nose cancer is extremely sensitive to radiotherapy and treatment is effective in three-quarters of the patients, about 20-30 per cent of high-risk patients will relapse in the lungs, liver and bones. Unfortunately, when the disease has spread to the other parts of the body, it is incurable, and accounts for death in 90 per cent of cases. We therefore need to optimise our ability to deliver more chemotherapy with in combination with chemo-radiotherapy in these at-risk patients,” says Dr Melvin Chua, a senior consultant radiation oncologist at NCCS, and a co-corresponding author of the study.

“On this note, people have tried to intensify treatment by applying chemotherapy upfront before chemo-radiotherapy in advanced nose cancer. We had previously shown that disease control and survival are improved using a triple drug combo, but such a treatment is extremely toxic and therefore it is rarely being used,” he adds.

The NCCS and SYSUCC therefore conducted a randomised controlled phase 3 clinical trial to investigate using another chemotherapy regime upfront – a doublet combo of gemcitabine and cisplatin with concurrent chemo-radiotherapy, and compare head-to-head against the current standard treatment of chemo-radiotherapy alone, in newly-diagnosed locally advanced nose cancer patients.

Gemcitabine-cisplatin was used here given that this regime is the first-line treatment in patients with recurrent nose cancer that has spread to other parts of the body.

This multi-centre trial was conducted among 12 sites in China and recruited a total of 480 high-risk cases. They found that using this combination, they observed one of the highest disease control and survival rates reported to-date of 85.3 per cent and 94.6 per cent respectively, at 3-years post-treatment, versus 76.5 per cent and 90.3 per cent respectively, for those who received the standard of care. This improved survival was primarily due to a lower proportion of patients recurring in other parts of the body.

Treatment was also well tolerated. More than 90 per cent of patients completed the three cycles of induction chemotherapy, and all patients completed radiotherapy after. Importantly, severe late complications due to treatment were not increased with the more intensive treatment, although there was an increase in low blood counts, nausea and vomiting and liver function abnormalities during treatment.

These results have now established a new standard of care in patients with locally advanced nose cancer. Induction gemcitabine and cisplatin plus chemo-IMRT is a first-line treatment option in these patients.

With the success of this trial, NCCS seeks to foster a deeper collaboration within the multi-centre collaborative trial network to run more novel trials in this high-risk locally advanced nose cancer disease space.

This clinical trial was partly supported by the National Medical Research Council Singapore’s Clinician-Scientist Award and the Duke-NUS Oncology Academic Program Proton Research Program.

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APBN Editorial Calendar 2019
January:
Taiwan Medical tourism
February:
Marijuana as medicine — Legal marijuana will open up scientific research
March:
Driven by curiosity
April:
Career developments for researchers
May:
What's cracking — Antibodies in ostrich eggs
June:
Clinical trials — What's in a name?
July:
Traditional Chinese medicine in modern healthcare — Integrating both worlds
Editorial calendar is subjected to changes.
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