This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harper, E. Articles by Garver, R. I. Search for Related Content PubMed PubMed Citation Articles by Harper, E. Articles by Garver, R. I., Jr.

Enhanced Efficacy of a Novel Controlled Release Paclitaxel Formulation (PACLIMER Delivery System) for Local-Regional Therapy of Lung Cancer Tumor Nodules in Mice¹

Lung Cancer Program and Division of Pulmonary/Allergy/Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007 [E. H., R. I. G.], and Guilford Pharmaceuticals, Inc., [W. D., R. G. L.], Baltimore, Maryland 21224

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.

This article has been cited by other articles:

				J. Liu, D. Meisner, E. Kwong, X. Y. Wu, and M. R. Johnston Translymphatic Chemotherapy by Intrapleural Placement of Gelatin Sponge Containing Biodegradable Paclitaxel Colloids Controls Lymphatic Metastasis in Lung Cancer Cancer Res., February 1, 2009; 69(3): 1174 - 1181. [Abstract] [Full Text] [PDF]

				G. H. Yoo, G. Subramanian, M. P. Piechocki, J. F. Ensley, O. Kucuk, O. E. Tulunay, F. Lonardo, H. Kim, J. Won, T. Stevens, et al. Effect of Docetaxel on the Surgical Tumor Microenvironment of Head and Neck Cancer in Murine Models Arch Otolaryngol Head Neck Surg, July 1, 2008; 134(7): 735 - 742. [Abstract] [Full Text] [PDF]

				A. Banzato, S. Bobisse, M. Rondina, D. Renier, F. Bettella, G. Esposito, L. Quintieri, L. Melendez-Alafort, U. Mazzi, P. Zanovello, et al. A Paclitaxel-Hyaluronan Bioconjugate Targeting Ovarian Cancer Affords a Potent In vivo Therapeutic Activity Clin. Cancer Res., June 1, 2008; 14(11): 3598 - 3606. [Abstract] [Full Text] [PDF]

				S. M. Azouz, J. Walpole, S. Amirifeli, K. N. Taylor, M. W. Grinstaff, and Y. L. Colson Prevention of local tumor growth with paclitaxel-loaded microspheres. J. Thorac. Cardiovasc. Surg., May 1, 2008; 135(5): 1014 - 1021. [Abstract] [Full Text] [PDF]

				K. L. Hennenfent and R. Govindan Novel formulations of taxanes: a review. Old wine in a new bottle? Ann. Onc., May 1, 2006; 17(5): 735 - 749. [Abstract] [Full Text] [PDF]

				A. R. Tzafriri, E. I. Lerner, M. Flashner-Barak, M. Hinchcliffe, E. Ratner, and H. Parnas Mathematical Modeling and Optimization of Drug Delivery from Intratumorally Injected Microspheres Clin. Cancer Res., January 15, 2005; 11(2): 826 - 834. [Abstract] [Full Text] [PDF]

				Z. Lu, T.-K. Yeh, M. Tsai, J. L.-S. Au, and M. G. Wientjes Paclitaxel-Loaded Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy Clin. Cancer Res., November 15, 2004; 10(22): 7677 - 7684. [Abstract] [Full Text] [PDF]

				K. W. Li, W. Dang, B. M. Tyler, G. Troiano, T. Tihan, H. Brem, and K. A. Walter Polilactofate Microspheres for Paclitaxel Delivery to Central Nervous System Malignancies Clin. Cancer Res., August 1, 2003; 9(9): 3441 - 3447. [Abstract] [Full Text] [PDF]