The combination of gemcitabine and radiotherapy is a promising combined modality therapy. However, the clinical application of this combination has to be implemented carefully because of an increased toxicity to normal tissues. A body of experimental evidence shows that gemcitabine is a potent radiosensitizer in vitro and in vivo. The observations so far indicate that various mechanisms are responsible for the radiosensitizing effect. Although it is often difficult to transfer experimental data to the clinic, these studies offer the possibility to develop an improved schedule of administration for patient treatment, based on rational evidence in tumor biology. In the current review, the preclinical data that support the use of gemcitabine as a radiosensitizing agent and the clinical trials that have been conducted to date are summarized. The Oncologist

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Ecteinascidin 743 (ET-743) is a new marine-derived agent with promising activity against a number of solid tumours. In four human tumour cell lines, the interaction between ET-743 and radiation was investigated in relation to the effects of ET-743 on the cell cycle, in vitro. Cell survival was measured based on quantitative staining of cellular protein by sulforhodamine B. A 24 h treatment with ET-743 before radiation resulted in a moderate increase in radiosensitivity in three out of four cell lines. Dose enhancement factors X1.8 were observed for concentrations resulting in 52, 46 and 30% cell kill in ECV304, H292 and CAL-27, respectively, whereas in A549 no radiosensitisation was observed (no significant increase in radiosensitivity). According to the combination index analysis, synergism was observed only in ECV304 and CAL-27 cells. A 24 h incubation with ET-743 resulted in a concentration-dependent G2/M block, which might explain the moderate radiosensitising effects in ECV304 and H292. The lack of radiosensitisation in A549 might be due to the S phase delay preceding the G2/M block at the moment of radiation, which only occurred in this cell line. In conclusion, ET-743 has moderate cell line-dependent radiosensitising properties; however, only when cytotoxic concentrations of ET-743 are used. In one of the four cell lines tested, no radiosensitisation was observed.