Lower risk of serious side-effects in trials of new targeted drugs

Patients in early clinical trials of new-style targeted cancer therapies appear to have a much lower risk of the most serious side-effects than with traditional chemotherapy, according to a new analysis. Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust analysed data from 36 Phase I trials run by the organisations' joint Drug Development Unit.

The study, published in August's Annals of Oncology, found the overall risk to patients of suffering a life-threatening side-effect was around seven times less than for traditional cytotoxic agents.

Most new cancer drugs developed over recent years are targeted agents, which attack the specific genetic or molecular faults driving cancer growth, rather than one-size-fits-all chemotherapeutics, which kill all rapidly dividing cells.

Recent studies have shown that patient response rates in Phase I trials of new-generation targeted drugs are approximately two-fold higher than for old-style drugs. But until now, the risk of side-effects to patients taking part in early stage trials of new-style drugs has been unclear.

Senior author Dr Rhoda Molife, a medical oncologist and senior investigator in Phase I clinical trials in the Drug Development Unit of The Institute of Cancer Research and The Royal Marsden, said: "Our study found that the risk of developing a serious side-effect in a Phase I trial of a targeted drug was relatively low, compared with previous analyses of similar trials of old-style chemotherapies.

"The theory behind targeted drugs is that they should affect only cancer cells that have a specific fault and spare healthy cells, which we hoped would lead to higher rates of efficacy and lower rates of side-effects. It's very pleasing that our study seems to back this up, at least in the context of Phase I trials."

"Importantly, we also identified characteristics that put patients at higher risk of these toxicities, including if they were sicker when joining the trial. This will help doctors make the right choices about who should be given new drugs in early stage clinical trials."

Scientists retrospectively analysed data from 687 patients treated at the Drug Development Unit of The Institute of Cancer Research and The Royal Marsden between January 2005 and December 2009. They had a range of cancer types, with gastrointestinal, gynaecological and sarcoma the most common.

The Drug Development Unit of The Institute of Cancer Research and The Royal Marsden is supported by the National Institute for Health Research Biomedical Research Centre for Cancer, and also receives funding from Cancer Research UK and the Experimental Cancer Medicine Centre network.

For targeted drugs, the most common toxicities were gastrointestinal - such as loss of appetite, diarrhoea and vomiting - and fatigue, while side-effects for cytotoxic drugs are generally haematological or cardiovascular in nature.

Patients were more likely to suffer side-effects if they were given a higher dose than that which the trial later found to be optimal, or if they were sicker when they joined the trial. The findings should help guide researchers in selecting patients for trials and improving trial design.

Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: "The discovery of targeted therapies is revolutionising the way we treat cancer, and is a key focus of our research here at The Institute of Cancer Research. Many of these drugs have individually transformed the care of certain cancers, but the strength of this study is that it helps confirm the validity of the overall approach."

Most Popular Now

Pfizer begins a Phase 1/2 study to evaluate respir…

Pfizer Inc. (NYSE:PFE) today announced that it has started a Phase 1/2 trial of its respiratory syncytial virus (RSV) vaccine candidate in healthy adult volunteers. RSV i...

Eczema drug effective against severe asthma

Two new studies of patients with difficult-to-control asthma show that the eczema drug dupilumab alleviates asthma symptoms and improves patients' ability to breathe bett...

Most popular vitamin and mineral supplements provi…

The most commonly consumed vitamin and mineral supplements provide no consistent health benefit or harm, suggests a new study led by researchers at St. Michael's Hospital...

AstraZeneca heads to 2018 ASCO Annual Meeting with…

AstraZeneca and MedImmune, its global biologics research and development arm, head to the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, US...

Tiny particles could help fight brain cancer

Glioblastoma multiforme, a type of brain tumor, is one of the most difficult-to-treat cancers. Only a handful of drugs are approved to treat glioblastoma, and the median ...

Novartis data at ASCO and EHA reinforce company's …

Novartis will present data from across its oncology portfolio at the upcoming 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) to be held June 1-5 ...

Spiolto® Respimat® enables greater physical activi…

Boehringer Ingelheim announced data which add to the growing body of evidence that show Spiolto® (tiotropium/olodaterol) Respimat® enables greater physical activity in pa...

Amgen Foundation and Harvard team up to offer free…

The Amgen Foundation and Harvard University today announced plans to launch a free online science education platform uniquely designed to level the playing field for aspi...

New approach to immunotherapy leads to complete re…

A novel approach to immunotherapy developed by researchers at the National Cancer Institute (NCI) has led to the complete regression of breast cancer in a patient who was...

Study demonstrates new treatment for severe asthma

Researchers from McMaster University and the Firestone Institute for Respiratory Health at St. Joseph's Healthcare Hamilton, together with colleagues at other partnering ...

The Pfizer Foundation announces $5 million in gran…

The Pfizer Foundation announced a new $5 million grant commitment to initiatives in low- and middle-income countries that provide family planning access and education for...

Study finds antioxidant-enriched vitamin reduces r…

Researchers at Children's Hospital Colorado (Children's Colorado) and the University of Colorado School of Medicine have found that taking a specially formulated antioxid...