Purpose: In vitro studies have demonstrated that sodium selenite in sufficient concentration and during sufficient time have a high tumoricidal capacity. This is found in many human cell types as leukemia cells, mesothelioma and non-small cell lung cancer cells. A minority of cell lines seem to be resistant. The question from a clinical point of view is: Is it possible with respect to toxicity to administer sodium selenite to patients in sufficient dose and during sufficient time to get responses in patients with cancer? We have performed first part of phase-1 study and found MTD of 10.2 mg/m2 if given as 10 daily infusions during 12 days. We have recorded limited anti-tumor effect in this treatment regimen. However, in vitro data suggest that low concentration of continuous exposure for 51 h is much more effective. Now we are planning to continue the phase-I trial with modified protocol.
More specific:
- Phase I: Find maximal tolerable dose with continuous infusion
- Phase II: Use MTD and study responses, if any
- Arms: Experimental: Selenite treatment
- In the first part of the study, cohorts of 3 patients receive sodium selenite iv, starting with a dose of 0.5 mg/m2. If no serious adverse event the next cohort is treated according to a dose escalation schedule and this part has been completed. In the modified protocol, a continuous infusion over 2 days will be administered.
- Assigned Interventions
- Drug: Sodium selenite (Introselen): Intravenous infusion daily for each week day during 2 weeks (10 infusions). After that chemotherapy during 6 weeks. Chemotherapy for each patients is the first line treatment, so chemotherapy differs among patients, with respect to which treatment a patient got as first line. Other Name: Introselen (Pharma Nord)
- Drug: Sodium selenite: Intravenous treatment as described above. Cohorts of 3 patient are given a fixed dose for daily treatment (started with 0.5 mg/m2) and if no grade 3 or 4 toxicity, a new cohort is started on a higher dose. The dose for next cohort is 50% higher than for the former cohort. If grade 3 or 4 toxicity is found in 1 patient, 3 more patients are included on the same dose and if one more patient has serious toxicity it is considered to high a dose and a dose in between the toxic dose and the one before is tested. Thus if 2 patients in 3-6 tested patients has serious toxicity by a certain dose, this dose is to high and the highest dose is considered the earlier tested dose. Other Name: Introselen (Pharma Nord)
