By Salma Khalik, The Straits Times

Two doctors at the National Cancer Centre Singapore (NCCS) have discovered a gene mutation in head and neck cancer patients that, for reasons as yet unknown, results in their responding well to a lung cancer drug.

At least one patient has survived a decade, instead of dying within a few months.

This mutation could possibly make squamous cell carcinoma (SCC) in other parts of the body also treatable.

A study of nine patients with SSC, who were given the drug, saw two in remission and three with their cancer under control. Four have died but their condition did improve and they survived longer than expected.

Without the treatment, the life expectancy was just six to nine months for these patients. But five are still alive today, more than three years after the study started.

The study by the NCCS team led by Dr Daniel Tan and Associate Professor Gopalakrishna Iyer was published in the high impact Nature Medicine journal last October.

It was accompanied by an editorial which said that while the mechanism was not yet understood, the findings could be used to predict a patient's response to the drug.

"In the era of precision medicine, every piece of information is important for increasing our capacity to predict treatment outcome," the editorial said.

Prof Gopal said their discovery, which he described as "a once in a lifetime find", came about purely by accident.

"It started with a clinical trial, 10 years ago "that failed miserably", as only two out of 38 patients responded to the drug. Given that poor response, there was no follow-up, although "for the two patients, their cancer tumour responded spectacularly", with one still alive today."

Assoc Prof Gopalakrishna Iyer, Head,
SingHealth Duke-NUS Head & Neck Centre

Laboratory tests of head and neck cancer tumours also found that a small minority reacted extremely well to the drug.

Dr Tan, in the meantime, was continuing to treat the two patients years after they should have died. Seeing them alive year after year kept him trying to figure out why.

In 2013, Prof Gopal met Dr Tan in the NCCS carpark and chatted about these "weird" cases.

"We decided there must be something there," Prof Gopal said. "So we started plugging at it."

They sequenced the DNA of the tumours and finally identified the mutation whose unusual behaviour was the trigger. It is found in about 5 per cent of patients with SCC.

They applied to the National Medical Research Council (NMRC) for funds to further their research but were turned down three times in 2016 and last year because it deemed the data "was insufficient or unconvincing".

But, with funds from donations to the NCCS, Prof Gopal and Dr Tan conducted the study on the nine patients, after getting approval from the centre's tumour board.

All nine were not suitable for conventional treatment like surgery and chemotherapy. But they could easily ingest the lung cancer drug Iressa.

Dr Tan said the drug costs more than $2,000 a month, but it goes off patent next year so the price will likely go down. The next step, he said, is a clinical trial of 50 patients.

Prof Gopal and Dr Tan also want to find out if this gene mutation makes SCC in other parts of the body, such as in the lungs, bladder or esophagus, also treatable with this drug.

They have again applied to the NMRC for funds - about $1.5 million - to pursue their reasearch.

NCCS clinical director, Associate Prof William Hwang, said their findings show "the high quality of research" from the centre.

"They have made NCCS proud and I hope they continue to get grants to support their work so that many more patients can benefit in future."

Assoc Prof William Hwang, Medical Director, NCCS

 

 

SOURCE: THE STRAITS TIMES.  SINGAPORE PRESS HOLDINGS LIMITED. REPRODUCED WITH PERMISSION.