Linked Life Data

1831442

Source:http://linkedlifedata.com/resource/pubmed/id/1831442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1991-9-24
pubmed:abstractText
Trimetrexate (TMTX), a potent inhibitor of the enzyme dihydrofolate reductase, was shown to be more active than its analogue, Methotrexate, against murine and human tumor cell lines in vitro and in vivo. We conducted two sequential phase I studies using a single bolus injection of TMTX every 14 days (Schedule A) and a weekly x 3 schedule every 4-6 weeks (Schedule B). Twenty-seven patients were treated on Schedule A with a TMTX dose range of 5 mg/m2 to 450 mg/m2 and 23 patients were treated on Schedule B with a TMTX dose range of 50 mg/m2 to 200 mg/m2. The dose limiting toxicity was myelosuppression on both schedules. The development of hematological toxicity was highly variable at different dose levels and within the same patient at a particular dose level. The nadir of blood counts was reached by Day 8 to 10 on the single dose schedule with recovery by Day 14. On Schedule B, the nadir granulocyte count occurred on Day 14 while platelet count was generally lowest by Day 20; the blood counts usually recovered 7 to 10 days after the last dose. Other common side-effects includes skin toxicity and stomatitis which were worse on the weekly schedule. Less common toxicities included mild nausea and vomiting, diarrhea, and transient deterioration in renal and hepatic functions. The occurrence of toxicity was not related to the extent of prior treatment, liver metastases, or accumulation of third space fluids. Based on our results, we recommend a starting TMTX dose for Phase II studies of 200 mg/m2 every 2 weeks or 100 mg/m2 to 125 mg/m2 on the weekly schedule.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0167-6997
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
199-206
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Phase I studies of trimetrexate using single and weekly dose schedules.
pubmed:affiliation
Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston.
pubmed:publicationType
Journal Article, Clinical Trial