Phase I trial of selenium plus chemotherapy in gynecologic cancers.

Purpose: Preclinical studies performed in our laboratory have shown that high-dose selenium inhibits the development of carboplatin drug resistance in an ovarian cancer mouse xenograft model. Based on these data, as well as the potential serious toxicities of supranutritional doses of selenium, a phase I trial of a combination of selenium/carboplatin/paclitaxel was designed to determine the maximum tolerated dose, safety, and effects of selenium on carboplatin pharmacokinetics in the treatment of chemo-naive women with gynecologic cancers. Correlative studies were performed to identify gene targets of selenium.

A Model of the Development of Cisplatin Resistance in Human Small Cell Lung Cancer Xenografts.

Background/aim: To study the prevention of chemotherapy resistance, we have previously designed models of drug-resistant ovarian cancer. We here report an in vivo model of cisplatin-resistant small cell lung cancer (SCLC).

Materials And Methods: Mice bearing H526 SCLC xenografts received intraperitoneal pretreatment with a sub-effective cisplatin dose (0.

Prevention of carboplatin-induced resistance in human ovarian tumor xenografts by selenite.

Background/aim: We have been exploring a prevention approach to the problem of drug resistance which develops during ovarian cancer chemotherapy. We have previously described an in vivo model of the development of resistance to the chemotherapy drug cisplatin in xenografts, and the prevention of this resistance by selenium compounds. However, a different platinum-based drug, carboplatin, is frequently utilized in ovarian cancer treatment.

Selenite enhances and prolongs the efficacy of cisplatin treatment of human ovarian tumor xenografts.

Background/aim: Our earlier studies on ovarian tumor xenografts provide evidence that co-treatment with selenite prevents the development of resistance to single-treatment using the drug cisplatin. However, these studies did not reflect the repetitive schedule of clinical chemotherapy. We hypothesized that selenite can enhance the effectiveness of cisplatin during the course of repeated treatments, reflecting clinical practices.