CPT-11-induced delayed-onset diarrhea is caused by a secretory mechanism with an exudative component. Early combined treatment with loperamide and acetorphan seems effective in controlling the diarrheal episodes.

SummaryRhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxicity, in mice-bearing a MDA-MB231 Luc+ tumor, orthotopically transplanted, after a daily oral administration at the dose of 10 mg/kg/d. Interestingly, an antagonism was observed when cisplatin was administered as a single i.p. injection 1 week after the end of the Re-diselenoether administration. In an effort to gain insight of the mechanisms of action of Re-diselenoether complex, interaction with 9-methylguanine as a nucleic acid base model was studied. We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.Electronic supplementary materialThe online version of this article (doi:10.1007/s10637-015-0265-z) contains supplementary material, which is available to authorized users.

Our results are in agreement with the in vitro data concerning the extensive binding of oxaliplatin to plasma proteins and RBCs. They also reveal a strong negative correlation between free drug plasma availability and renal function, with a corresponding positive correlation between clearance of the plasmatic platinum and renal function. Thus, renal impairment entails a greater overall exposure to platinum in the plasma. However, this study failed to elicit any relationship between moderate renal impairment and the acute toxicity associated with oxaliplatin.

Oxaliplatin (L-OHP) is the only platinum compound to show activity in colorectal cancer. We evaluated the cytotoxicity of L-OHP on four human cancer cell lines and its influence on the cell cycle, when treated during long exposure (72 h) and different post-incubation times (24 or 72 h). We used a panel of cell lines: HT29 (colon cancer), MCF7 (breast cancer), Hela (uterine cervix) and A549 (lung adenocarcinoma). Inhibition concentration (IC)(50) was assessed by MTT assay. Cell cycle modifications were determined using dual parameter bromodeoxyuridine and propidium iodide. L-OHP yielded a superior cytotoxicity on HT29 and MCF7 relative to Hela and A549 after treatment, the post-incubations demonstrate that growth inhibition was irreversible for HT29 and Hela cell lines contrary to MCF7 and A549. The main effects of L-OHP are G2/M cell cycle arrest and transient S phase delay. Taken together, L-OHP treatment results on HT29, MCF7 and Hela, are in favor of lengthening the infusion duration to patients during further clinical trials.