Linked Life Data

12394266

Source:http://linkedlifedata.com/resource/pubmed/id/12394266

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-10-23
pubmed:abstractText
We sought to define the tolerance of 9-amino-20(S)-camptothecin (9-AC) when given by the i.p. route to patients with cancer in the peritoneal cavity consisting of nodules that did not exceed 1 cm in maximum diameter. 9-AC was given in six fractions over 12 days, at doses ranging from 1.25 to 13.5 mg/m(2) in cycles repeated every 28 days. Dose escalations after the first two dose levels took place in cohorts of three patients, with expansion of the dose level once a dose-limiting toxicity (DLT) was encountered. All patients had blood and i.p. pharmacokinetic (PK) analysis during cycle 1 of each dose level. Topoisomerase (Topo) I signal was serially measured in peripheral blood mononuclear cells (PBMCs) in blood and cells collected in i.p. cytologic washings. Twelve patients received 31 cycles of 9-AC. Tolerance to repeated i.p. drug administration was generally excellent. The DLT was neutropenia encountered at the highest dose level in two patients, whereas the dose of 9 mg/m(2) was well tolerated. The DLTs were associated with peak plasma levels ranging from 47 to 81 ng/ml and also depletion of Topo I in PBMCs. The i.p.:plasma AUC ratio (+/-SD) was 11.5 (+/-3.8). Two patients had objective evidence of clinical benefit and only one of seven patients deemed evaluable for response had progressive disease. We conclude that i.p. 9-AC demonstrates excellent local tolerance at a dose and schedule associated with evidence of systemic effects. A dose of 9 mg/m(2)/cycle administered in a schedule of six divided fractions is suitable for further evaluation against tumors involving primarily the peritoneal cavity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0959-4973
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
819-25
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Phase I and pharmacologic study of i.p. 9-aminocamptothecin given as six fractions over 14 days.
pubmed:affiliation
NYU Cancer Institute, Division of Medical Oncology, New York University School of Medicine, New York, NY 10016, USA. muggif01@gcrc.med.nyu.edu
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Clinical Trial, Phase I