Whitehouse P A, Mercer S J, Knight L A, Di Nicolantonio F, O'Callaghan A, Cree I A
Department of Histopathology, Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK.
Br J Cancer. 2003 Dec 15;89(12):2299-304. doi: 10.1038/sj.bjc.6601403.
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.
晚期或转移性疾病在食管癌和胃癌以及结直肠癌中都很常见,尽管进行了姑息化疗,5年生存率仍很低。我们使用改良的基于三磷酸腺苷(ATP)的体外肿瘤化学敏感性测定法(ATP-TCA),研究了胃肠道肿瘤对吉西他滨联合丝裂霉素C(GeM)的敏感性。评估了41例结直肠癌和22例食管癌及胃癌的肿瘤组织。在大多数测试样本中,GeM联合用药显示出不同但明确的活性。结果表明,在所测试的60%的结直肠肿瘤(35例中的21例)和38%的食管胃癌肿瘤(13例中的5例)中,GeM在临床可达到的浓度范围内实现了>95%的抑制。我们未发现肿瘤来源细胞同时或序贯暴露于这两种药物时在敏感性上有任何显著差异。这项研究的结果表明,GeM可能是治疗晚期胃肠道恶性肿瘤的一种有用联合用药。