P3-024: Sodiumselenite in the treatment of lung cancer

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Resistance to chemotherapy is a major obstacle to improved survival in NSCLC and SCLC. In vitro, selenite in fairly moderate concentration kills most lung cancer cell lines. We have started a clinical study on selenite to patients with chemotherapy resistant lung cancer. In vitro studies of lung cancer, mesotelioma and leucemia cell lines have demonstrated that sodiumselenite in doses above 5 micromol/L induces apoptosis in most cell lines. It is accomplished in a different manner compared to clinically used cytotoxic drugs, since there seems to be especially the drug resistant cell lines that are sensitive to selenite. An enzyme thioredoxin reductase seems to be involved in the process. High doses of this enzyme protects against the oxidative stress produced by cytotoxic drugs but not to selenite. An additive effect of selenite and chemotherapy is also seen. One further finding makes sodium selenite interesting in this context. During the seventies sodiumselenite with Se75 was used as a tumor seeking tracer for scintigraphy, making it probable that a favourable Se gradient might be found clinically. The maximal tolerable dose (MTD) of sodium selenite is not known. Therefore we have started with an ordinary phase I study to define MTD. Selenium is given in daily doses during a five week period. After that a response evaluation is performed and patients not acquiring a complete response are two weeks after the selenite stop given chemotherapy. When MTD is found we will proceed with an ordinary phase II study with response as the primary endpoint. Serum and tumour samples will be taken both in the phase I and II studies to study dose-effect relationship and to seek predictive factors among others with microarray expression in untreated and treated tumour cells. The first patient in the phase I study has just gone through the selenite treatment without side effects. The next two on the first treatment level are just going to start. Further results from the phase I study will be presented at the meeting. If selenite could be given in sufficient doses to kill tumor cells with acceptable side effects it would probably be a cheap and useful complement to cytotoxic drugs.