SINGAPORE — Mention cancer treatments, and chemotherapy and radiotherapy — along with their harsh side effects such as hair loss, vomiting and low blood count — usually come to mind.

Not any more. A new generation of “smart drugs”, known as targeted therapies, is changing the way cancer is being treated.

Only this year alone, new targeted therapies have been made available for local patients suffering from HER2-positive metastatic breast cancers and late-stage lung cancer with epidermal growth factor receptor (EGFR) mutations.

Metastatic cancer refers to cancer that has spread from its original site to other parts of the body. Both of these cancer types are particularly aggressive and are likely to progress more rapidly.

In Singapore, lung and breast cancers were the top cancer killers among men and women, respectively, from 2008 to 2012, said the National Disease Registries Report.

Unlike conventional cancer treatment such as chemotherapy, which affects rapidly dividing cells in the body, these smart drugs target only specific mutations in cancer cells, said Dr Tan Sing Huang, senior consultant at the Department of Haematology-Oncology at the National University Cancer Institute, Singapore.

“Targeted therapies are more selective than chemotherapy in that they are less likely to affect the surrounding normal cells while in the process of attacking cancerous cells,” he said.

“Instead, they interrupt the pathways that are involved in the growth and spread of cancer to slow or halt cancer progression.

Dr Tan Sing Huang explained that some of these targeted therapies work by using antibodies to attack certain receptors on the cancer cells.

In addition, there are drugs which work by using small molecules to enter the cancer cell and disrupt it. There are also other drugs that prevent new blood vessels in the tumour from forming, thus starving the tumour of blood supply.

KEEPING BREAST CANCER CELLS UNDER CONTROL

About one in five breast cancer cases in Singapore is HER2-positive. HER2-positive cancer possesses an excess of HER2 receptors on the cancer cell surface, which can lead to uncontrolled and more aggressive cancer growth, said Dr Tan Sing Huang.

The new smart drugs, pertuzumab and trastuzumab emtansine, are designed to target these HER2 receptors and are administered via intravenous infusion.

“Before the era of targeted therapies, HER2-positive metastatic breast cancer patients were limited to traditional chemotherapy and anti-hormonal drugs. Patients with this disease had a very poor prognosis,” said Dr Tan Sing Huang.

“However, targeted therapies against HER2 have altered the natural course of the disease. Patients’ survival has been significantly extended.”

BLOCKING MUTATED LUNG CANCER GENES

Similarly, a new targeted therapy, afatinib, has improved survival outcomes for patients suffering from late-stage lung cancer with the EGFR gene mutation.

The oral tablet is the latest EGFR-TKI (tyrosine-kinase inhibitor), which works by blocking the actions of the mutated EGFR gene, thereby blocking the growth and spread of the lung cancer cells.

Two large-scale phase three trials have shown that patients treated with afatinib lived for almost a year before their tumour started to grow again, compared with over half a year for those on chemotherapy, said Dr Tan Yew Oo, consultant medical oncologist and hematologist with Singapore Oncology Consultants.

The EGFR gene mutation is found in about six in 10 patients who do not smoke or are light smokers.

This particular type of lung cancer is three times more common among Asians, compared with our Western counterparts, added Dr Tan Yew Oo.

MORE TOLERABLE SIDE EFFECTS

As a result of its selectivity, one of the main advantages of targeted therapy is that patients experience fewer or more tolerable side effects.

Said Dr Tan Sing Huang: “In comparison, chemotherapy affects rapidly dividing cells. It not only affects cancerous cells, but also other normal cells in the body such as our bone marrow, hair cells or the cells lining the gastrointestinal tract.”

Dr Tan Yew Oo added: “For instance, patients on chemotherapy for lung cancer may experience harsh side effects including nausea, vomiting, hair loss, low blood count, bleeding and infections.

“On the other hand, those on the new EGFR-TKIs may have rash, nail changes, diarrhoea, skin discolouration and changes in liver function tests, which are generally better tolerated.”

The experts are optimistic about personalised cancer treatments. Said Dr Tan Yew Oo: “We are at the dawn of an era where we can personalise treatment and design new drugs by looking for new molecular targets in the cancer.

“We can now better understand how these cancers grow and spread, and how to kill the cancer cells based on their particular characteristics.”