Enhanced efficacy of a novel controlled release paclitaxel formulation (PACLIMER delivery system) for local-regional therapy of lung cancer tumor nodules in mice.
The efficacy of systemic chemotherapy for non-small cell lung cancer (NSCLC) has improved with newer agents. However, the response rates and prolonged survival times achieved by chemotherapy remain modest, and these small gains are obtained at the cost of significant toxicity. In this study, the efficacy of a controlled release formulation of paclitaxel was compared with conventional paclitaxel in animals with human lung cancer xenografts. Paclitaxel (10%) was encapsulated in a proprietary polymer in the form of microspheres (PACLIMER Delivery System). Tumor nodules comprised of two different cell lines (A549 and H1299) were treated by a single i.p. or intratumoral administration of conventionally formulated paclitaxel or a single intratumoral injection of the PACLIMER Delivery System. In vitro testing demonstrated that paclitaxel was released slowly from the microspheres with >80% released after 90 days. Direct comparison of the highest dose for all formulations (24 mg/kg) showed that for nodules comprised of either NSCLC cell line, growth of the PACLIMER Delivery System-treated nodules were inhibited significantly more than the groups treated with conventional paclitaxel or the vehicle controls. Tumor volume doubling times for A549 and H1299 nodules treated with PACLIMER Delivery System were 60 and 35 days, respectively, compared with 10 and 11 days, respectively, in the nodules treated with the conventional paclitaxel by intratumoral administration. We conclude that intratumoral administration of the PACLIMER Delivery System may substantially increase the efficacy of paclitaxel for the therapy of local-regional NSCLC.
Harper
E
E
Lung Cancer Program and Division of Pulmonary/Allergy/Critical Care Medicine, University of Alabama at Birmingham, 35294-0007, USA.
Dang
W
W
Lapidus
R G
RG
Garver
R I
RI
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006131:Growth Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D006131:Growth Inhibitors; D017239:Paclitaxel