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 Google Scholar Articles by Milenic, D. E. Articles by Brechbiel, M. W. PubMed PubMed Citation Articles by Milenic, D. E. Articles by Brechbiel, M. W.

Multimodality Therapy: Potentiation of High Linear Energy Transfer Radiation with Paclitaxel for the Treatment of Disseminated Peritoneal Disease

Authors’ Affiliations: ¹ Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, and ² Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH; ³ Biometric Research Branch, National Cancer Institute, Bethesda, Maryland; and ⁴ Hematology and Oncology, College of Medicine, Ohio State University, Columbus, Ohio

Requests for reprints: Diane E. Milenic, NIH, 10 Center Drive, MSC-1088, Building 10, Room 1B40, Bethesda, MD 20892. Phone: 301-496-9086; Fax: 301-402-1923; E-mail: dm71q{at}nih.gov.

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

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

Results: Paclitaxel (300 or 600 µg) followed 24 h later with [²¹³Bi]trastuzumab (500 µCi) provided no therapeutic enhancement. Paclitaxel (300 µg) administered concurrently with [²¹³Bi]trastuzumab or [²¹³Bi]HuIgG resulted in median survival of 93 and 37 days, respectively; no difference was observed with 600 µg 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 µg) 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 µg) followed by [²¹³Bi]trastuzumab. Studies were also conducted investigating paclitaxel administered 24 h before, concurrently, or 24 h after [²¹²Pb]trastuzumab (10 µCi). The 300 µg paclitaxel 24 h before radioimmunotherapy (RIT) failed to provide benefit, whereas 600 µg 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.