| Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications. | |
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MedLine Citation:
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PMID: 15774788 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer. |
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Authors:
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Alphonse G Taghian; Rita Abi-Raad; Sherif I Assaad; Adrian Casty; Marek Ancukiewicz; Eren Yeh; Peryhan Molokhia; Khaled Attia; Timothy Sullivan; Irene Kuter; Yves Boucher; Simon N Powell |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 23 ISSN: 0732-183X ISO Abbreviation: J. Clin. Oncol. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-18 Completed Date: 2005-04-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 1951-61 Citation Subset: IM |
Affiliation:
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Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ataghian@partners.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Combined Chemotherapy Protocols
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therapeutic use* Breast Neoplasms / drug therapy* Chemotherapy, Adjuvant Doxorubicin / administration & dosage Drug Administration Schedule Extracellular Fluid / drug effects Female Humans Menopause Middle Aged Oxygen Consumption / drug effects Paclitaxel / administration & dosage |
| Grant Support | |
ID/Acronym/Agency:
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P50 CA89393/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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23214-92-8/Doxorubicin; 33069-62-4/Paclitaxel |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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