Scientists attack 'breakthrough' cancer drugs

Exaggerated claims are being made for new cancer treatments that are not justified by the evidence, scientists warned yesterday.

Drugs hailed as breakthrough treatments for cancer, Britain's biggest cause of death, may be less effective and cause more harm than suspected, they said.

A sharp increase in the number of trials being halted prematurely to deliver rapid results is undermining confidence in the drugs.

Public demand for access to new treatments, allied to the pharmaceutical companies' eagerness to bank profits, creates pressure on researchers to terminate trials as soon as a drug reveals a benefit. But that can be before the full results are in.

A review of 25 trials of cancer drugs that had been stopped early during the past decade because they had started to show a benefit to patients, found more than half (14) had been halted in the past three years. Of those, 11 were used to support an application for a drug licence in Europe or in the US, researchers discovered.

One of the research team, Giovanni Apolone, from the Mario Negri Institute for Pharmacological Research in Milan, said: "This suggests a commercial component in stopping trials prematurely. We are aware that trials stopped early because they are showing benefit may result in the identification of promising new treatments for patients.

"However, findings obtained in this way require subsequent confirmation. Without such evidence, unsafe and ineffective drugs could be marketed and patients' health could well be jeopardised."

The drugs tested in the trials that were stopped early include some of the biggest new discoveries in cancer therapy, touted as heralding a new golden age in treatment. They include Herceptin (trastuzumab) for breast cancer, Avastin (bevacizumab) for bowel and kidney cancer, Campto (irinotecan) for lung and bowel cancer, Sutent (sunitinib) for kidney and gastrointestinal cancer, Nexavar (sorafenib) for kidney cancer, and TaxolCarbo (carboplatin) for ovarian and lung cancer.

Dr Apolone said it could take years for the long-term benefits or dangerous side-effects of a drug to become evident, but the average duration of the 25 trials stopped early was just 30 months. Five had enrolled less than 40 per cent of the planned number of patients.

Only 4 per cent of the trials were halted because of serious adverse effects but Dr Apolone said the main worry was that early stopping exaggerated the beneficial effects.

Writing in the online edition of Annals of Oncology, the researchers say: "If a trial is evaluating long-term efficacy of a treatment of conditions such as cancer, short-term benefits – no matter how significant statistically – may not justify early stopping. Data on disease recurrence and progression, drug resistance, metastasis, or adverse events, all factors that weigh heavily in the benefit/risk balance, could easily be missed."

Stuart Pocock, professor of medical statistics at the London School of Hygiene and Tropical Medicine, who had no involvement in the study, said all trials should have independent monitoring committees of experts to advise on when they should be stopped early.

Statistically, stopping trials that showed early evidence of benefit while allowing the rest to run their full course would skew the overall results and exaggerate the benefits, he said.

"Overall, there is an underlying bias towards exaggeration [of the results]. We can pretty reliably claim there is exaggeration going on. This is not as sober an environment as it should be. It has an aura of hot-headedness about it."

Professor David Kerr, editor of Annals of Oncology, said researchers faced a dilemma. "If we see an effective cancer drug, it is our duty to get it into the clinic as quickly as possible. But we must not run down the quality of the evidence to support that drug."

Cancer drug trials stopped early

Herceptin

Breast cancer – two trials started 2001 and 2003

Avastin

Bowel cancer – trial started 2005

Campto

Lung cancer – trial started 1995

Sutent

Gastrointestinal cancer – trial started 2003

Nexavar

Kidney cancer – trial started 2003

TaxolCarbo