ABSTRACT
We conducted a double-blind, randomized crossover study to compare the toxicity and antiemetic efficacy of the 5-hydroxytryptamine3 receptor antagonist batanopride with that of metoclopramide in 21 chemotherapy-naive patients receiving at least 70 mg/m2 cisplatin. The study was terminated when hypotension was observed following the infusion of batanopride at other institutions testing similar drug schedules. Although we observed no hypotension following treatment with batanopride in this trial, we did note asymptomatic prolongation of the corrected QT interval (QTc), PR interval, and QRS complex on the EKG in the batanopride arm. Of 15 evaluable patients, 8 experienced less than or equal to 2 episodes of emesis within 24 h of the first batanopride infusion, whereas 9/15 subjects experienced less than or equal to 2 emetic episodes following the administration of metoclopramide. Overall, the evidence suggests that this dosing schedule for batanopride may be too toxic for clinical use.
Subject(s)
Antiemetics/therapeutic use , Cisplatin/adverse effects , Metoclopramide/analogs & derivatives , Metoclopramide/therapeutic use , Vomiting/prevention & control , Antiemetics/administration & dosage , Antiemetics/adverse effects , Double-Blind Method , Drug Tolerance , Humans , Infusions, Intravenous , Metoclopramide/administration & dosage , Metoclopramide/adverse effects , Time Factors , Vomiting/chemically inducedABSTRACT
A microtiter assay was developed to monitor cytotoxic activity of drugs alone and in combination at varying ratios on a single plate. Combinations of metoclopramide or sodium thiosulfate with cis-diamminedichloroplatinum(II) (cisplatin) were evaluated in vitro and in vivo for cisplatin cytotoxicity to murine leukemia L1210. The in vitro assay indicated that metoclopramide did not interfere with cisplatin-induced cytotoxicity and confirmed previously reported inhibition of cisplatin activity by sodium thiosulfate. The drug combinations were also evaluated in vivo for antitumor activity and the results of these studies corroborated the in vitro results.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia L1210/drug therapy , Animals , Cells, Cultured , Cisplatin/administration & dosage , Drug Evaluation , Metoclopramide/administration & dosage , Mice , Thiosulfates/administration & dosageABSTRACT
A microtiter cytoxicity assay using mammalian cell lines was developed to detect fermentation-derived antitumor agents. Two murine (AKR, B16) and four human (HTB-31, KB, MOSER, RCA) cell lines were used to evaluate 2000 fermentation broth supernatants. The mammalian cell lines tested showed different spectra for fermentation broth activity, as predicted by responses to known antitumor agents. Data were compared with standard antimicrobial assays historically used to screen for antitumor activity for this set of 2000 broths. There was an overlap of approximately 30% of broths identified as containing in vitro bioactivity by the two assay systems. Sixty-three antimicrobially active broths were tested for activity in P388 in vivo; the cytotoxicity assay predictive rate (40%) was twice that of the antimicrobial assays.
