Anticancer agent – erlotinib

Epidermal growth factor receptor (EGFR), a Type I receptor tyrosine kinase, plays a crucial role in modulating cell differentiation. It is overexpressed in many forms of cancer, where it can lead to an increase in the tumour's potential to metastasise, so inhibiting EGFR signalling has potential as a method of treating cancers. Various tyrosine kinase inhibitors have been developed, mainly reversible competitors with ATP for binding to the tyrosine kinase's intracellular catalytic domain.

Erlotinib is such a drug, which was first discovered by Pfizer, but is now being co-developed by OSI Pharmaceuticals, Genentech and Roche.

Numerous Phase I trials evaluating its effectiveness in combination with other anticancer agents have been carried out. Sixteen patients were given intravenous erlotinib alongside docetaxel. One patient with nasopharyngeal cancer has had a near complete response, and the disease has been stabilised for at least four months in several patients with bladder, non small cell lung (NSCL), ovarian, skin and stomach cancers.1 A further Phase I trial combined erlotinib with paclitaxel and carboplatin in nine patients. One patient had a near complete response, two a minor response, and two had their disease stabilised for more than three months.2

The drug's efficiacy has been investigated in a multicentre single arm open label Phase II trial in patients with advanced squamous cell head and neck cancer that had recurred. It was well tolerated, with adverse events including rash, diarrhoea, nausea, vomiting, headache and fatigue. A total of 78 patients were evaluable for response; 10 experienced partial response, 23 had their disease stabilised, and the disease progressed in 45 patients.3

A randomised, controlled Phase III trial is now being carried out to evaluate its antitumour efficacy in combination with paclitaxel and carboplatin in around a thousand patients with NSCL cancer, and a further Phase III trial is under way in around 1,200 NSCL cancer patients in combination with gemcitabine and cisplatin.