Anti-cancer drugs
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
A multicenter, double-blind comparison of i.v. and oral administration of ondansetron plus dexamethasone for acute cisplatin-induced emesis. Ondansetron Acute Emesis Study Group.
A total of 530 patients were treated in this multicenter, double-blind, double-dummy, parallel group study to compare the anti-emetic efficacy and safety of a once daily ondansetron oral regimen with a once daily i.v. dosing regimen over a 24 h period, administered to patients prior to receiving cisplatin (50 mg/m2 or greater) chemotherapy. Patients were randomized to receive a single dose of ondansetron plus dexamethasone given either orally (ondansetron 24 mg and dexamethasone 12 mg, n=262) or i.v. (ondansetron 8 mg and dexamethasone 20 mg, n=268). Complete control of emesis (i.e. no emetic episodes, no rescue and no premature withdrawal) was achieved for 85% of patients (224 of 262) in the oral group and 83% (223 of 268) in the i.v. group. ⋯ There were no statistically significant differences between the two groups for any of the assessments of efficacy, which included time to first emetic episode, number of emetic episodes and the worst grade of nausea occurring over the 24 h study period. Once daily ondansetron oral and i.v., in combination with dexamethasone, was well tolerated in this study. In conclusion, once daily oral ondansetron 24 mg plus dexamethasone is equally effective in the control of emesis and nausea induced by highly emetogenic chemotherapy as once daily ondansetron 8 mg i.v. plus dexamethasone.
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To evaluate potential synergistic interactions between topoisomerase I (Topo I) inhibitors, i.e. camptothecin (CPT) and topotecan (TPT), and chemotherapeutic agents known to be active in treatment of brain tumors, in vitro studies were conducted with human glioma and medulloblastoma cell lines. Tumor cells were exposed to CPT or TPT alone or in combination with cisplatin, 4-hydroperoxycyclophosphamide (4-HC), BCNU or etoposide (VP-16). Cytotoxicity was assessed by colony formation assays. ⋯ By contrast, antagonistic interactions were observed after administration of CPT with BCNU or VP-16. Treatment of U251 cells with CPT and cisplatin produced synergistic or antagonistic cytotoxicity depending on the dose combination used. These findings support a role for pharmacokinetic analysis in multiagent phase 11 trials involving Topo I inhibitors and have important implications for clinical trial design strategies.