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Clinical trial defines new standard treatment for advanced Nasopharyngeal Cancer

Nasopharyngeal cancer (NPC) is the eighth most frequent cancer in males in Singapore. The disease predominantly affects the Chinese population, 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.

Concurrent chemo-radiotherapy has been the standard treatment for this subgroup of high-risk patients. This usually entails precise high-dose radiotherapy using intensity modulated radiotherapy (IMRT) techniques, followed by cisplatin (chemotherapy).

Although NPC is extremely sensitive to radiotherapy and treatment is effective in three-quarters of the patients, chances of a relapse are high. "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," explains Dr Melvin Chua, a senior consultant radiation oncologist at National Cancer Centre Singapore (NCCS).

To improve treatment outcomes for at-risk patients, NCCS and Sun Yat-sen University Cancer Center (SYSUCC) in Guangzhou, China, collaborated on a clinical trial. Findings from the trial established a new global standard treatment for high-risk locally advanced NPC.

"We need to optimise our ability to deliver more chemotherapy in combination with chemo-radiotherapy in these patients. Researchers have tried to intensify treatment by applying chemotherapy before chemo-radiotherapy in advanced NPC. We had previously shown that disease control and survival are improved using a triple drug combo, but such treatment is extremely toxic and therefore rarely used," says Dr Melvin Chua, who is also a co-corresponding author of the study.

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. This was compared to the current standard treatment of chemo-radiotherapy alone, in newly-diagnosed locally advanced NPC patients. Gemcitabine-cisplatin was used given that this regime is the first-line treatment in patients with recurrent NPC that has spread to other parts of the body.

Using the new combination, the multi-centre trial 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. A significant improvement over 76.5 per cent and 90.3 per cent respectively, for those who received the current standard treatment. This improved survival was primarily due to a lower proportion of patients having the cancer recurring in other parts of the body. Treatment was also well tolerated.

Importantly, the more intensive treatment did not increase severe late complications, 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 NPC. Induction gemcitabine and cisplatin plus chemo-radiotherapy is a first-line treatment option for 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. 

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