Anticancer agent – dalotuzumab

Another fertile area of anticancer research is the insulin-like growth factor 1 receptor pathway, which is involved in malignancy and mediating drug resistance. One way this might be disrupted is by blocking growth factor signalling at the interface between ligand and receptor, and Merck is developing the monoclonal antibody dalotuzumab for this indication, under licence from Pierre Fabre.¹

Its safety and efficacy as monotherapy were investigated in a Phase II trial in 25 metastatic neuroendocrine tumour patients.² They were given 10mg/kg of the antibody intravenously once a week. Although five of the patients achieved stable disease for at least 24 weeks, no antitumour activity was observed, indicating that it is not likely to succeed as monotherapy in patients with these types of tumours. The most common side-effect was hyperglycaemia, which could be managed via medication.

More promising results were seen in a Phase I/II trial in 28 patients with advanced, untreated pancreatic cancer, in combination with gemcitabine or gemcitabine plus erlotinib.³ They were escalated in two dose levels, with all given 1,000mg/m² of gemcitabine, plus either 5 or 10mg/kg of the antibody, and some given 100mg daily doses of erlotinib. Six patients achieved a partial response, in five of whom it was sustained, and eight stable disease. Again, side-effects included hyperglycaemia, plus neutropoenia and thrombocytopenia, each of which occurred in five or six patients.

A randomised Phase II trial is under way.

references

1. L. Goetsch et al. Int. J. Cancer 2005, 113, 316

2. D.L. Reidy et al. J. Clin. Oncol. 2010, 28 (15, suppl.), Abst. 4163

3. M.M. Javle et al. J. Clin. Oncol. 2010, 28 (15, suppl.), Abst. 4039