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Monday 25th June 2018

Some tumours resistant to Pfizer drug

29th October 2010

Most lung cancer patients who are treated with a drug manufactured by Pfizer, crizotinib, saw some improvement, although there are signs of resistance in some tumours, a new study shows.


Researchers led by Eunice Kwak from the Massachusetts General Hospital reported in the New England Journal of Medicine that the drug shrank the tumours of 57% of patients.

A further 33% saw their condition stabilise during therapy with crizotinib.

In all, it is likely that 72% of study participants would have enjoyed a further six months without their disease worsening, the study concluded.

The Phase 1 clinical trial found high response rates in patients with ALK-positive lung cancer.

Mace Rothenburg of Pfizer said doctors could be a step closer to the development of precision, personalised cancer treatments that target specific genetic factors driving certain tumours.

But a second study at the University of Tokyo led by Young Lim Choi followed a patient who developed two independent mutations that made the tumour resistant to crizotinib.

The university's Hiroyuki Mano said that the manifestation of resistance was not surprising, and that other so-called ALK inhibitors had the same problem to some degree.

Mano said that while it was bad news that some people might not be helped by the new drugs, the additional data about resistant mutations would be helpful in designing the next generation of ALK inhibitors.

The information could be used to make a drug with wider applicability in future.

Pfizer has said it plans to begin submitting data for approval of the drug to the U.S. drug regulatory body early in 2011.

Crizotinib targets cells that turn cancerous when a fused gene -- EML4-ALK -- is formed from the merger of two separate genes.

Around 3-5% of people with non-small-cell lung cancer get this kind of cancer. In the United States, that adds up to around 10,000 cancer patients annually.

The study participants had all had one round of chemotherapy already.

Normally, second-round chemotherapy only works in around 10% of cases, according to Bengt Hallberg and Ruth Palmer of Umea University in Sweden.

In about 40% of patients, mild-to-moderate side-effects like nausea and diarrhoea were reported.

In one case reported in the NEJM, the drug, also known as PF-02341066, helped a 44-year-old man with a rare inflammatory myofibroblastic tumour that had the ALK mutation.

However, the study led by James Butrynski of the Dana-Farber Cancer Institute in Boston found that the drug did not appear to help a younger patient without the mutation.

AstraZeneca's Iressa and Roche's Tarceva are already known to be effective against cancer in patients with a mutation activating the epidermal growth factor receptor (EGFR).

Lung cancer kills around 1.2 million people annually, out of a total of 1.61 million cases worldwide every year, according to the International Agency for Research on Cancer.

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