29 Sep 2011
By: NG WAN CHING
Mr Raymond Lee celebrated his 66th birthday last week.
And it was something worth celebrating.
Almost three years ago, he had been diagnosed with stage 4 liver cancer which had spread to his abdominal lymph nodes.
Doctors told him it was inoperable. He had one big tumour (8cm by 5cm by 9cm) on the right lobe of the liver and numerous small ones on the left lobe. Without medication, he could expect to live four months.
With sorafenib, a new drug for advanced liver cancer, he could expect to live five to six months.
It was a huge shock.
But there was a ray of hope.
The surgeon who had just given him the bad news recommended that he join a new clinical trial at the Singapore General Hospital (SGH).
It was to study the effect of combining two known therapies for liver cancer.
They were sorafenib and selective internal radiation therapy (SIRT), in which tiny beads carrying a radioactive material are injected into an artery which carries them to the tumour (see facing page).
The impact of this was assessed by comparing the results with known outcomes from other studies of patients on only sorafenib or only SIRT.
Today, Mr Lee is one of the longest surviving patients of that trial.
Its lead researcher, Professor Pierce Chow, senior consultant surgeon in the department of general surgery at SGH, said the results of the trial on 35 patients were very encouraging and proved his instincts right, when he and his team analysed them early this year.
The mean survival time for those with inoperable liver cancer which had not spread outside of the liver was 20.6 months compared with known data of 14.3 months for those on sorafenib alone and eight months for those on a placebo.
For those with inoperable liver cancer which had spread outside of the liver or invaded blood vessels, it was 8.2 months, compared with 5.6 months for those on sorafenib alone and 4.1 months for those on placebo.
Both were significantly longer survival times compared with patients on sorafenib alone or on placebo.
Prof Chow presented the study results yesterday at the 3rd Biennial Congress of the Asian Pacific Hepato Pancreato Biliary Association in Melbourne.
He said: “Until recently, there was little you could do for those with liver cancer that cannot be surgically removed. There was no chemotherapy or drugs which could help.”
It was particularly grim because fewer than two in 10 patients with liver cancer are eligible for surgery at the time of diagnosis.
Between 400 and 500 people here are diagnosed with liver cancer each year. It is the third most fatal cancer among men here and the fifth most fatal cancer among women here.
The three main causes of liver cancer are liver cirrhosis (scarring) caused by hepatitis B and C infections and alcoholic liver disease, in which the liver becomes inflamed and swollen.
But in June 2007, the first clinical trials for sorafenib showed that patients could live three months longer on average with the drug than on a placebo.
At around the same time, Prof Chow was reading reports on SIRT.
“Early trials and retrospective studies showed that SIRT was shrinking tumours and tumours were responding dramatically,” he said.
His instinct was that patients would benefit from combining a systemic therapy like sorafenib with an efficacious local-regional therapy like SIRT.
“You have a therapy which targets the tumour directly, followed by a systemic drug which targets the body’s system to ensure that cancer cells are contained – should be good, right? The only way to know is to do a trial,” he said.
He also liked the fact that SIRT uses beta radiation, which has a short maximum range of 11mm.
“That’s ideal for internal radiation therapy. It will kill tumour cells but is less likely to hurt surrounding non-cancerous tissues,” he said.
He applied for a grant and started his trial in 2008. He recruited 35 patients, 12 of whom had locally advanced cancer and 23 in whom the cancer had spread outside of the liver or into blood vessels. One patient was not assessed. He received SIRT but not sorafenib because he started bleeding from the cancer that had spread to his lungs.
Prof Chow is in the midst of a larger trial to find out which of the two therapies – sorafenib or SIRT – should be used first for patients with inoperable liver cancers.
A total of 360 patients from 20 hospitals and cancer centres in 13 countries will be recruited for this study. It will have funds of about $10.2 million, of which $8.5 million was a gift from Australian medical device company Sirtex Medical and $1.65 million, to be disbursed over five years, came from the National Medical Research Council.
Mr Lee, who was diagnosed in November 2008, joined Prof Chow’s earlier trial and was treated with SIRT in January 2009.
“I stayed in hospital for a few days after the radiation therapy to make sure everything was all right,” said Mr Lee.
The treatment did not hurt. A few weeks later, he was put on sorafenib pills until September 2009. He had almost no side effects except for a few small blisters on his calves.
“My hair did not drop out, my appetite remained the same,” said the retired civil servant and father of two.
Although the combined treatment did not shrink his tumours by very much, his disease has remained stable. The tumours are slightly smaller and have not grown.
“I just carry on with my life. I do my gardening, am out and about, have lunch with my friends. I have no discomfort,” he said.
His only symptom at the beginning was what he thought was gastric pain.
“I went for a check-up. The doctor did a colonoscopy and a gastroscopy. Then he sent me for an ultrasound scan for kidney stones. That was when they discovered this huge tumour in my liver,” said Mr Lee.
But he never lost hope. And he has even learnt a new life skill. “I can now take public transport,” he said with some pride. Because he goes to the hospital so often and has to stay a few hours each time, he seldom drives there.
“Parking is hard to find and so expensive. So I take a bus or the MRT, which I never did before,” he said with a laugh.
“It’s been almost three years and I’m still here. I go for my regular check-ups every three months. There’s nothing life-threatening at the moment. I enjoy my time with my family. Life is good.”
SELECTIVE INTERNAL RADIATION THERAPY (SIRT)
This uses tiny resin microspheres that are loaded with yttrium-90, a radioisotope that emits pure beta radiation.
The radiation from yttrium-90 is largely confined to a tissue depth of 2 to 3mm.
After injection into the artery supplying blood to the tumours, the microspheres are trapped in the tumour’s vascular bed, where they destroy the tumour cells by delivering the beta radiation.
The radiation is targeted and contained within the patient’s body. After 14 days, most of its effect would have occurred.
The radiation is directed to the liver and does not affect other organs in the body.
SIRT has a one-time cost of $25,000.
SORAFENIB
It is a molecular, targeted therapy drug. It interferes with the signals that control cancer cell growth or multiplication.
It works by cutting off the blood supply to the cancer and slipping inside the cancer cells and sabotaging pathways important for cell growth.
The drug is also used to treat kidney cancer.
It costs $10,000 a month.
Email: wanching@sph.com.sg
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