Multimodality therapy: potentiation of high linear energy transfer radiation with paclitaxel for the treatment of disseminated peritoneal disease.

Abstract

PURPOSE:

Studies herein explore paclitaxel enhancement of the therapeutic efficacy of alpha-particle-targeted radiation therapy.

EXPERIMENTAL DESIGN:

Athymic mice bearing 3 day i.p. LS-174T xenografts were treated with 300 or 600 microg paclitaxel at 24 h before, concurrently, or 24 h after [213Bi] or [212Pb]trastuzumab.

RESULTS:

Paclitaxel (300 or 600 microg) followed 24 h later with [213Bi]trastuzumab (500 microCi) provided no therapeutic enhancement. Paclitaxel (300 microg) administered concurrently with [213Bi]trastuzumab or [213Bi]HuIgG resulted in median survival of 93 and 37 days, respectively; no difference was observed with 600 microg paclitaxel. Mice receiving just [213Bi]trastuzumab or [213Bi]HuIgG or left untreated had a median survival of 31, 21, and 15 days, respectively, 23 days for just either paclitaxel dose alone. Paclitaxel (300 or 600 microg) given 24 h after [213Bi]trastuzumab increased median survival to 100 and 135 days, respectively. The greatest improvement in median survival (198 days) was obtained with two weekly doses of paclitaxel (600 microg) followed by [213Bi]trastuzumab. Studies were also conducted investigating paclitaxel administered 24 h before, concurrently, or 24 h after [212Pb]trastuzumab (10 microCi). The 300 microg paclitaxel 24 h before radioimmunotherapy (RIT) failed to provide benefit, whereas 600 microg extended the median survival from 44 to 171 days.

CONCLUSIONS:

These results suggest that regimens combining chemotherapeutics and high linear energy transfer (LET) RIT may have tremendous potential in the management and treatment of cancer patients. Dose dependency and administration order appear to be critical factors requiring careful investigation.

• Authors: Diane E Milenic, Kayhan Garmestani, Erik D Brady, Kwamena E Baidoo, Paul S Albert, Karen J Wong, Joseph Flynn, Martin W Brechbiel
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 16 Pg. 5108-15 (Aug 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18698028 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunoglobulin G
• Radiation-Sensitizing Agents
• Trastuzumab
• Paclitaxel

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Combined Modality Therapy
• Female
• Humans
• Immunoglobulin G (administration & dosage)
• Mice
• Mice, Nude
• Neoplasms, Experimental (pathology, therapy)
• Paclitaxel (administration & dosage)
• Peritoneal Neoplasms (secondary, therapy)
• Radiation-Sensitizing Agents (administration & dosage)
• Radioimmunotherapy (methods)
• Trastuzumab
• Xenograft Model Antitumor Assays