Abstract
BackgroundThe choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC.MethodsTumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mitomycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison.ResultsThe GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs.ConclusionEx vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy.
Highlights
The choice of drugs for treatment of advanced gastric cancer (GC) is empirical
The HER2 binding monoclonal antibody trastuzumab improves the median overall survival by 2 - 3 months in advanced gastric or gastrooesophageal junction cancer when added to standard chemotherapy, provided the tumor cells express significant amount of the antibody target [8]
Other targeted drugs (TDs), e g everolimus, sorafenib, sunitinib and bortezomib have been tried in small early clinical trials as single agents or combined with cytotoxic drugs and show varying results in advanced GC, from no to some activity [9,10,11,12]
Summary
The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. A fluoropyrimidine combined with a platinum is mostly used and was previously reported to provide a median overall survival within clinical trials of approximately 11 months [3]. The HER2 binding monoclonal antibody trastuzumab improves the median overall survival by 2 - 3 months in advanced gastric or gastrooesophageal junction cancer when added to standard chemotherapy, provided the tumor cells express significant amount of the antibody target [8]. Optimal use of the currently established drugs is associated with an overall survival (OS) within clinical trials of approximately 14 - 16 months [8,13]
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