Experimental Therapeutics

British Journal of Cancer (2003) 89, 2299–2304. doi:10.1038/sj.bjc.6601403 www.bjcancer.com
Published online 12 December 2003

Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C

P A Whitehouse1, S J Mercer1, L A Knight1, F Di Nicolantonio1, A O'Callaghan2 and I A Cree1 on behalf of the Portsmouth Upper GI and Colorectal Cancer Multidisciplinary Teams

  1. 1Department of Histopathology, Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK
  2. 2Portsmouth Oncology Centre, St Mary's Hospital, Portsmouth PO3 6AD, UK

Correspondence: IA Cree, E-mail: ian.cree @port.ac.uk

Received 17 March 2003; Revised 12 September 2003; Accepted 22 September 2003.

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Abstract

Advanced or metastatic disease is common in both oesophagogastric and colorectal cancers, with poor 5-year survival despite palliative chemotherapy. We have investigated the sensitivity of gastrointestinal tumours to gemcitabine in combination with mitomycin C (GeM), using a modified ex vivo ATP-based tumour chemosensitivity assay (ATP-TCA). Tumour material from 41 colorectal and 22 oesophagogastric cancers were assessed. The GeM combination showed variable but definite activity in most of the samples tested. The results show that GeM achieves >95% inhibition at concentrations within the range achievable clinically in 60% of colorectal tumours (21 out of 35) and 38% of oesophagogastric tumours (five out of 13) tested. We did not identify any significant difference in sensitivity using concurrent or sequential exposure of tumour-derived cells to these two drugs. The results from this study suggest that GeM may be a useful combination in the treatment of advanced gastrointestinal malignancy.

Keywords:

colorectal cancer, oesophageal cancer, gemcitabine, mitomycin C, chemotherapy, ATP-TCA