title: Preclinical activity of an i.v. formulation of rubitecan in IDD-P against human solid tumor xenografts.
abstract: An i.v. formulation of rubitecan (9-nitrocamptothecin) was evaluated in five human solid tumor xenograft models. Rubitecan in IDD-P, a particulate suspension of the insoluble analog, produced significant tumor growth delay in athymic nude mice bearing A375 melanoma, and MX-1 breast, SKMES non-small-cell lung, Panc-1 pancreatic and HT29 colon carcinomas. The activity of i.v. rubitecan was similar or somewhat superior to those of i.p. regimens with the reference drugs, irinotecan and topotecan. Tumor sensitivity to rubitecan in IDD-P was MX-1>A375>SKMES >Panc-1>HT29. Some complete regression responses were seen with MX-1, A375 and SKMES tumors treated with 2.5 mg/kg on a schedule of two 5-day dosing cycles separated by 2 drug-free days. In nude mice, the MTD of rubitecan in IDD-P lies between 2 and 2.5 mg/kg on this schedule; antitumor efficacy was achieved with doses between 2.5 and 1.25 mg/kg. Dosing with 6.6 mg/kg rubitecan in IDD-P on intermittent schedules (4- or 7-day intervals) was tolerated, but less efficacious, when tested in the A375 model. The good responses obtained with rubitecan in IDD-P suggest it could be used clinically in circumstances where an i.v. formulation offers advantages to oral or aerosol formulations.
authors.affiliation: SuperGen, Inc, Dublin, CA 94568, USA. sands@erols.com
authors.forename: Howard
authors.initials: H
authors.lastname: Sands
authors.forename: Awadhesh
authors.initials: A
authors.lastname: Mishra
authors.forename: Johanna D
authors.initials: JD
authors.lastname: Stoeckler
authors.forename: Beth
authors.initials: B
authors.lastname: Hollister
authors.forename: Shih-Fong
authors.initials: SF
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D002214:Capsules; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D006801:Humans; D007275:Injections, Intravenous; D020714:Maximum Tolerated Dose; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010316:Particle Size; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; C079905:rubitecan; D002166:Camptothecin