Smart drugs to battle cancer


COMBATING LATE-STAGE BREAST CANCER: Dr Yap is treating Ms T’s cancer as part of the CLEOPATRA trial at NCCS.

MEDICAL advances have taken the battle against cancer to a point where some very select forms of the disease can be managed, even if not cured, almost like a chronic, long-term illness.

But such types of targeted treatment for individual cancer conditions – sometimes called personalised treatment or stratified medicine – remain a work in progress.

The weapon in this fight is a range of smart drugs – molecular drugs which don’t cure but can potentially stop the cancer from growing, said Dr Toh Han Chong, Head and Senior Consultant, Department of Medical Oncology, National Cancer Centre Singapore (NCCS).

“In the last 10 to 20 years, there has been an explosion in our understanding of what makes cancers grow and how we can switch off the signals that cause the cancers to grow,” he said.

He likened these attempts to blocking the battery socket in a toy bunny, which stops the bunny from moving.

“What many people have uncovered are the circuits that cause the bunny to go on and on, which represents the ever growing cancer.

They’ve been able to block the place where the battery fits into the socket of the bunny.

They’ve been able to use a surrogate drug to block the path where the battery is supposed to go in and, by doing so, slow the cancer or stop it from growing, thereby causing the cancer cell to die.

Terrorists However, eradicating cancer requires a meticulous and methodical approach.

“Cancer is many kinds of diseases.

Even within one cancer, you can see how diverse it can be.

And if you look at all the different cancers, some are very fast moving and others very slow growing.

By that token alone, we are obviously dealing with a challenging set of problems.

“If you think of cancer as elusive terrorists, you’ll know it is a frustrating and long war because you usually can’t get rid of all of them once they have left their hiding place and spread across the world.

Let’s say a surgical strike wipes out all the terrorists hiding out in the mountain.

You think you’ve eradicated them.

But then, there’s this lone terrorist on a plane toLibya, another crossing the border toPakistanand yet another flying to theUnited Kingdom.

You don’t always know where they are.

“You normally can’t fight every single cancer cell that has spread, just as it’s hard to defeat every single terrorist in a cell somewhere deep in a jungle.

You just have to contain them.

You have to create a drug and a strategy that can contain them systemically,” Dr Toh said.

A poster child of the new molecular drugs is Glivec – which has transformed the treatment of chronic myelogenous leukaemia (CML) and gastrointestinal stromal tumours (GISTs).

“For example, if GIST has spread all over the body, the usual survival is less than a year.

But nowadays, with this drug, you could easily be alive four to five years later.

This is an example of how the goal is not to go for the cure, but to go for containment and converting cancer into a chronic disease.

” Another drug is pertuzumab, a treatment which has passed initial safety assessments and is completing phase three trial.

Known as CLEOPATRA (which stands for Clinical Evaluation Of Pertuzumab And Trastuzumab), the study evaluates whether the drug can be part of “a first-line regimen” in patients with a certain type of metastatic breast cancer.

This new drug, developed by Genentech, a member of the Roche Group, could join the ranks of “smart” cancer drugs that target malignancies based on their molecular characteristic.

CONTAINING CANCER: Battling cancer is like fighting a terrorist - it can attack any part of the body and it is impossible to fight every single cancer cell, said Dr Toh Han Chong (right).

Roche has said it plans to submit pertuzumab for approval with healthcare authorities, as the trial is showing that patients with advanced breast cancer using the new drug are living much longer without the disease getting worse – in what is termed progression- free survival.

If successful, CLEOPATRA will add to the world’s arsenal on what seems to be mission impossible – the war on cancer.

In the protracted battle against the deadly skin cancer melanoma, two drugs hurdled Food and Drug Administration approval in theUSthis year – ipilimumab and vemurafenib.

Ipilimumab, marketed as Yervoy from Bristol-Myers Squibb Co (BMS), aims to boost the patient’s immune system to fight advanced stage melanoma, while vemurafenib, known as Zelboraf from Roche andJapan’s Daiichi Sankyo Co, works by blocking a genetic mutation that is seen to help the melanoma grow.

Both drugs showed exceptional success in patients with advanced melanoma.

These were huge achievements in the field of targeted therapy.

Roche and BMS are also planning to study whether the two drugs may be more effective if used in combination.

Still, the hope a new drug brings remains tempered by the emotional and mental anxiety of living life as a cancer survivor.

“What cancer survivors fear is a relapse.

Every time a cancer relapses and the battle of drugs against cancer begins again, the chances of further drugs working get less and less because of ensuing resistance,” said Dr Toh.

Over time, a cocktail of drugs for one cancer may become ineffective as the cancer changes and/or builds up resistance to the treatment, usually prompting a new set of drug therapy.

Many cancer patients live longer and live in much better shape than they might have otherwise, by moving on to available new treatments once their current cocktail loses its potency.

The fact that more drugs are now available means treatments can be combined and sequenced to keep the cancer in check.

Mrs T, a breast cancer survivor, is taking part in the CLEOPATRA study at NCCS.

She doesn’t pay for her cancer treatment because she agreed to participate in the clinical trial of pertuzumab.

But once “smart drugs” reach the market, they can get expensive, especially without insurance.

The NCCS is one of several medical centres worldwide participating in CLEOPATRA, which is a randomised, doubleblind, placebo-controlled trial to eliminate any bias from doctors or patients if they know they are receiving the new drug.

Mrs T’s stage four breast cancer appears to have stabilised since she began her treatment.

Dr Yap Yoon Sim, Senior Consultant, Department of Medical Oncology, who is treating Mrs T, said the signs are encouraging.

“The problem is that we can’t always tell patients that they have been cured of the cancer because, in general, stage four for most cancers is not curable.

But with improvement in treatment options, it is not impossible.

At the same time, if we say that they are totally cured, it may not be true, because one day it may come back,” Dr Yap said.

At stage four, Mrs T’s cancer had spread from her breast to her liver.

She opted to take part in the CLEOPATRA trial to give herself the chance of winning her fight against cancer, although she does not know if she is getting the drug because it s a double-blind trial.

Mrs T found cancer in her left breast when she was 53 years old.

She underwent a mastectomy, chemotherapy and radiation therapy, and seven months after her diagnosis, she was in remission.

That was 2002.

Seven years later in early 2009, despite vigilant mammograms and full blood count checks, the cancer returned – it had metastasised into her liver.

It was stage four cancer.

Mrs T, who chose to be anonymous, then decided to participate in CLEOPATRA – a trial of a new drug known as pertuzumab to combat late-stage breast cancer.

Mrs T’s therapy includes chemotherapy – at least for her first nine treatments until she complained of serious numbness in her hands and feet – and Herceptin, another “smart” antibreast cancer drug.

CLEOPATRA is her third “drug”, but she doesn’t know if she is among half of the 808 patients in the global clinical trial who are receiving pertuzumab.

Every three weeks, Mrs T goes to National Cancer CentreSingaporefor her intravenous treatment of anti-cancer drugs.

Every nine weeks, she sits for a CT scan of her chest and abdomen and radionuclide imaging to check the status of her cancer.

In late August, Mrs T was up to her 45th intravenous treatment since she relapsed over two years ago.

She is 62 years old now and her condition has stabilised.

“Even though it is a trial, it’s a double blind, so you don’t know if you get the new drug.

Only the company knows.

I thought, ‘Why not?’ Maybe the new drug will have more breakthrough.

This trial, they pay for everything… and if I get the new drug, then I would be getting better that much more,” she said.

• This story was first published in Singapore Health, Nov/Dec 2011.