| Phase I study of hepatic arterial degradable starch microspheres and mitomycin. | |
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MedLine Citation:
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PMID: 3928157 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intraarterial administration of 40-microns degradable starch microspheres (DSM) in a drug solution can temporarily retard flow of the drug-blood column through the arteriolar-capillary bed and lead to increased local drug deposition. Premonitory to Phase II-III efficacy studies applying this concept to regional therapy, it was necessary to determine the DSM dose to use. Patients with hepatic cancers were treated with varying doses of DSM with mitomycin C coadministered into the hepatic artery to define a dose of DSM which produces acceptable toxicity with maximal hepatic drug deposition as determined by a reduction in systemic mitomycin C exposure. Comparison of six patients receiving 6 ml of DSM (6 X 10(6) particles/ml) with ten patients receiving 15 ml showed a lower incidence and decreased severity of acute toxicity in terms of nausea/vomiting (16% versus 50%) and right upper quadrant hepatic pain (none versus 40%) with 6 ml of DSM. Reduction in systemic mitomycin C exposure evaluated by decrements in the area under the concentration curve in peripheral blood with time due to DSM was similar in both groups. Another seven patients were treated with escalating doses of DSM concurrently with 5 mg of mitomycin C. Although all seven patients tolerated 6 ml of DSM, higher doses (9 ml, 12 ml, 15 ml) led to incremental patient drop-out due to severe, acute right upper quadrant pain with only two patients able to receive 15 ml of DSM. In these patients, 6 ml of DSM appeared nearly equivalent to higher doses in terms of systemic exposure to mitomycin C. Eleven additional patients were evaluated for tolerance to repeated 6-ml dosing of DSM. Four patients had epigastric pain correlating with flow to the stomach demonstrated by nuclide angiography. The seven patients with no pain and no flow to stomach were treated with good tolerance for three-plus courses. Thus, 6 ml of DSM appear to be appropriate for Phase II-III studies. |
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Authors:
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W D Ensminger; J W Gyves; P Stetson; S Walker-Andrews |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 45 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1985 Sep |
Date Detail:
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Created Date: 1985-09-30 Completed Date: 1985-09-30 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4464-7 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Dose-Response Relationship, Drug Drug Evaluation Female Hepatic Artery Humans Infusions, Intra-Arterial* Male Middle Aged Mitomycin Mitomycins / administration & dosage* Neoplasms / drug therapy* Starch / administration & dosage*, adverse effects |
| Grant Support | |
ID/Acronym/Agency:
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5-MO-1-RR-42/RR/NCRR NIH HHS; CA33825/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Mitomycins; 50-07-7/Mitomycin; 9005-25-8/Starch |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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