title: Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C.
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.
authors.affiliation: Department of Histopathology, Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Whitehouse
authors.forename: S J
authors.initials: SJ
authors.lastname: Mercer
authors.forename: L A
authors.initials: LA
authors.lastname: Knight
authors.forename: F
authors.initials: F
authors.lastname: Di Nicolantonio
authors.forename: A
authors.initials: A
authors.lastname: O'Callaghan
authors.forename: I A
authors.initials: IA
authors.lastname: Cree
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000093542:Gemcitabine