Clinical aspects of drug delivery to tumors.
This report describes our experience on enhancement of drug delivery to solid tumors. Results of our preclinical and clinical studies including a randomized prospective phase III trial have validated the concept that enhanced drug delivery can significantly improve the treatment efficacy of intravesical mitomycin C therapy of superficial bladder cancer. The report further describes the roles of interstitial space, drug removal by capillaries, tissue structure and tissue composition on drug distribution. In general, drug distribution favors interstitial space and vasculature, with little penetration in muscles. The transport of highly protein-bound drugs such as paclitaxel and doxorubicin in a solid tumor is retarded by a high tumor cell density and enhanced by drug-induced apoptosis. Results of in vitro studies using solid tumor histocultures and in vivo studies using tumor-bearing animals demonstrate that the delivery of highly protein-bound drugs to tumor can be enhanced using a pretreatment that induces apoptosis and reduces cell density, and by using treatment schedules designed to take advantage of these drug-induced changes in tumor tissue composition.
Au
Jessie L-S
JL
College of Pharmacy and James Cancer Hospital and Solove Research Institute, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA. au.1@osu.edu
Jang
Seong H
SH
Wientjes
M Guill
MG
D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy*; D012107:Research Design; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D016685:Mitomycin